Abstract

The purpose of this study was to investigate cellular sources of autofluorescence signals in freshly isolated frog (Rana pipiens) retinas. Equipped with an ultrafast laser, a laser scanning two-photon excitation fluorescence microscope was employed for sub-cellular resolution examination of both sliced and flat-mounted retinas. Two-photon imaging of retinal slices revealed autofluorescence signals over multiple functional layers, including the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Using flat-mounted retinas, depth-resolved imaging of individual retinal layers further confirmed multiple sources of autofluorescence signals. Cellular structures were clearly observed at the PRL, ONL, INL, and GCL. At the PRL, the autofluorescence was dominantly recorded from the intracellular compartment of the photoreceptors; while mixed intracellular and extracellular autofluorescence signals were observed at the ONL, INL, and GCL. High resolution autofluorescence imaging clearly revealed mosaic organization of rod and cone photoreceptors; and sub-cellular bright autofluorescence spots, which might relate to connecting cilium, was observed in the cone photoreceptors only. Moreover, single-cone and double-cone outer segments could be directly differentiated.

© 2011 OSA

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. G. R. Jackson, C. Owsley, and C. A. Curcio, “Photoreceptor degeneration and dysfunction in aging and age-related maculopathy,” Ageing Res. Rev. 1(3), 381–396 (2002).
    [CrossRef] [PubMed]
  2. R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006).
    [CrossRef] [PubMed]
  3. B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
    [CrossRef] [PubMed]
  4. Y. Qin, G. Xu, and W. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006).
    [CrossRef] [PubMed]
  5. R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006).
    [CrossRef] [PubMed]
  6. R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007).
    [CrossRef] [PubMed]
  7. B. Chance, “Pyridine nucleotide as an indicator of the oxygen requirements for energy-linked functions of mitochondria,” Circ. Res. 38(5Suppl 1), I31–I38 (1976).
    [PubMed]
  8. S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
    [CrossRef] [PubMed]
  9. F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
    [PubMed]
  10. O. La Schiazza and J. F. Bille, “High-speed two-photon excited autofluorescence imaging of ex vivo human retinal pigment epithelial cells toward age-related macular degeneration diagnostic,” J. Biomed. Opt. 13(6), 064008 (2008).
    [CrossRef] [PubMed]
  11. Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry 46(34), 9674–9684 (2007).
    [CrossRef] [PubMed]
  12. A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
    [PubMed]
  13. D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
    [CrossRef] [PubMed]
  14. J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
    [CrossRef] [PubMed]
  15. A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
    [CrossRef] [PubMed]
  16. Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
    [CrossRef] [PubMed]
  17. H. Hillman, T. Hussain, and P. Sartory, “Autofluorescence of isolated unfixed rabbit Deiters’ neurons and surrounding neuroglial clamps,” Experientia 29(9), 1113–1115 (1973).
    [CrossRef] [PubMed]
  18. K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
    [CrossRef] [PubMed]
  19. J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
    [CrossRef] [PubMed]
  20. J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
    [CrossRef] [PubMed]
  21. K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008).
    [CrossRef] [PubMed]
  22. F. Romero-Borja, K. Venkateswaran, A. Roorda, and T. Hebert, “Optical slicing of human retinal tissue in vivo with the adaptive optics scanning laser ophthalmoscope,” Appl. Opt. 44(19), 4032–4040 (2005).
    [CrossRef] [PubMed]
  23. C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
    [CrossRef] [PubMed]
  24. Q. Q. Wu, C. H. Chen, and Y. Koutalos, “All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion,” Biophys. J. 91(12), 4678–4689 (2006).
    [CrossRef] [PubMed]
  25. M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
    [CrossRef] [PubMed]
  26. M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
    [CrossRef] [PubMed]
  27. J. M. Bueno, E. J. Gualda, and P. Artal, “Adaptive optics multiphoton microscopy to study ex vivo ocular tissues,” J. Biomed. Opt. 15(6), 066004 (2010).
    [CrossRef] [PubMed]
  28. E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt. 15(2), 026007 (2010).
    [CrossRef] [PubMed]
  29. L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
    [CrossRef]
  30. P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
    [CrossRef] [PubMed]
  31. Y. C. Li, C. Strang, F. R. Amthor, L. Liu, Y. G. Li, Q. X. Zhang, K. Keyser, and X. C. Yao, “Parallel optical monitoring of visual signal propagation from the photoreceptors to the inner retina layers,” Opt. Lett. 35(11), 1810–1812 (2010).
    [CrossRef] [PubMed]
  32. Y. B. Zhao and X. C. Yao, “Intrinsic optical imaging of stimulus-modulated physiological responses in amphibian retina,” Opt. Lett. 33(4), 342–344 (2008).
    [CrossRef] [PubMed]
  33. Q. X. Zhang, J. Y. Wang, L. Liu, and X. C. Yao, “Microlens array recording of localized retinal responses,” Opt. Lett. 35(22), 3838–3840 (2010).
    [CrossRef] [PubMed]
  34. X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008).
    [CrossRef] [PubMed]
  35. Y. G. Li, Q. X. Zhang, L. Liu, F. R. Amthor, and X. C. Yao, “High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation,” Opt. Express 18(7), 7210–7218 (2010).
    [CrossRef] [PubMed]
  36. Y. G. Li, L. Liu, F. Amthor, and X. C. Yao, “High-speed line-scan confocal imaging of stimulus-evoked intrinsic optical signals in the retina,” Opt. Lett. 35(3), 426–428 (2010).
    [CrossRef] [PubMed]
  37. X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005).
    [CrossRef] [PubMed]
  38. X. C. Yao and J. S. George, “Near-infrared imaging of fast intrinsic optical responses in visible light-activated amphibian retina,” J. Biomed. Opt. 11(6), 064030 (2006).
    [CrossRef] [PubMed]
  39. X. C. Yao and J. S. George, “Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals,” Neuroimage 33(3), 898–906 (2006).
    [CrossRef] [PubMed]
  40. P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(03), 519–532 (1994).
    [CrossRef] [PubMed]
  41. S. E. Nilsson, “An electron microscopic classification of the retinal receptors of the leopard frog (Rana pipiens),” J. Ultrastruct. Res. 10(5-6), 390–416 (1964).
    [CrossRef] [PubMed]
  42. P. A. Liebman and G. Entine, “Visual pigments of frog and tadpole (Rana pipiens),” Vision Res. 8(7), 761–775, IN1–IN7 (1968).
    [CrossRef] [PubMed]
  43. V. Ramamurthy and M. Cayouette, “Development and disease of the photoreceptor cilium,” Clin. Genet. 76(2), 137–145 (2009).
    [CrossRef] [PubMed]
  44. T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
    [CrossRef] [PubMed]

2011

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

2010

J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
[CrossRef] [PubMed]

J. M. Bueno, E. J. Gualda, and P. Artal, “Adaptive optics multiphoton microscopy to study ex vivo ocular tissues,” J. Biomed. Opt. 15(6), 066004 (2010).
[CrossRef] [PubMed]

E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt. 15(2), 026007 (2010).
[CrossRef] [PubMed]

Y. C. Li, C. Strang, F. R. Amthor, L. Liu, Y. G. Li, Q. X. Zhang, K. Keyser, and X. C. Yao, “Parallel optical monitoring of visual signal propagation from the photoreceptors to the inner retina layers,” Opt. Lett. 35(11), 1810–1812 (2010).
[CrossRef] [PubMed]

Q. X. Zhang, J. Y. Wang, L. Liu, and X. C. Yao, “Microlens array recording of localized retinal responses,” Opt. Lett. 35(22), 3838–3840 (2010).
[CrossRef] [PubMed]

Y. G. Li, Q. X. Zhang, L. Liu, F. R. Amthor, and X. C. Yao, “High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation,” Opt. Express 18(7), 7210–7218 (2010).
[CrossRef] [PubMed]

Y. G. Li, L. Liu, F. Amthor, and X. C. Yao, “High-speed line-scan confocal imaging of stimulus-evoked intrinsic optical signals in the retina,” Opt. Lett. 35(3), 426–428 (2010).
[CrossRef] [PubMed]

T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
[CrossRef] [PubMed]

2009

V. Ramamurthy and M. Cayouette, “Development and disease of the photoreceptor cilium,” Clin. Genet. 76(2), 137–145 (2009).
[CrossRef] [PubMed]

L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
[CrossRef]

J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
[CrossRef] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

2008

K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008).
[CrossRef] [PubMed]

P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
[CrossRef] [PubMed]

X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008).
[CrossRef] [PubMed]

Y. B. Zhao and X. C. Yao, “Intrinsic optical imaging of stimulus-modulated physiological responses in amphibian retina,” Opt. Lett. 33(4), 342–344 (2008).
[CrossRef] [PubMed]

O. La Schiazza and J. F. Bille, “High-speed two-photon excited autofluorescence imaging of ex vivo human retinal pigment epithelial cells toward age-related macular degeneration diagnostic,” J. Biomed. Opt. 13(6), 064008 (2008).
[CrossRef] [PubMed]

2007

Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry 46(34), 9674–9684 (2007).
[CrossRef] [PubMed]

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007).
[CrossRef] [PubMed]

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
[CrossRef] [PubMed]

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

2006

X. C. Yao and J. S. George, “Near-infrared imaging of fast intrinsic optical responses in visible light-activated amphibian retina,” J. Biomed. Opt. 11(6), 064030 (2006).
[CrossRef] [PubMed]

X. C. Yao and J. S. George, “Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals,” Neuroimage 33(3), 898–906 (2006).
[CrossRef] [PubMed]

Y. Qin, G. Xu, and W. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006).
[CrossRef] [PubMed]

R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006).
[CrossRef] [PubMed]

R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Q. Q. Wu, C. H. Chen, and Y. Koutalos, “All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion,” Biophys. J. 91(12), 4678–4689 (2006).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

2005

2004

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

2002

A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
[PubMed]

G. R. Jackson, C. Owsley, and C. A. Curcio, “Photoreceptor degeneration and dysfunction in aging and age-related maculopathy,” Ageing Res. Rev. 1(3), 381–396 (2002).
[CrossRef] [PubMed]

1995

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

1994

P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(03), 519–532 (1994).
[CrossRef] [PubMed]

1976

B. Chance, “Pyridine nucleotide as an indicator of the oxygen requirements for energy-linked functions of mitochondria,” Circ. Res. 38(5Suppl 1), I31–I38 (1976).
[PubMed]

1973

H. Hillman, T. Hussain, and P. Sartory, “Autofluorescence of isolated unfixed rabbit Deiters’ neurons and surrounding neuroglial clamps,” Experientia 29(9), 1113–1115 (1973).
[CrossRef] [PubMed]

1968

P. A. Liebman and G. Entine, “Visual pigments of frog and tadpole (Rana pipiens),” Vision Res. 8(7), 761–775, IN1–IN7 (1968).
[CrossRef] [PubMed]

1964

S. E. Nilsson, “An electron microscopic classification of the retinal receptors of the leopard frog (Rana pipiens),” J. Ultrastruct. Res. 10(5-6), 390–416 (1964).
[CrossRef] [PubMed]

Agopov, M.

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

Amthor, F.

Amthor, F. R.

Aoki, T.

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

Arend, O.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

Artal, P.

E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt. 15(2), 026007 (2010).
[CrossRef] [PubMed]

J. M. Bueno, E. J. Gualda, and P. Artal, “Adaptive optics multiphoton microscopy to study ex vivo ocular tissues,” J. Biomed. Opt. 15(6), 066004 (2010).
[CrossRef] [PubMed]

Bearelly, S.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Becker, W.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Bergmann, A.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Bille, J. F.

O. La Schiazza and J. F. Bille, “High-speed two-photon excited autofluorescence imaging of ex vivo human retinal pigment epithelial cells toward age-related macular degeneration diagnostic,” J. Biomed. Opt. 13(6), 064008 (2008).
[CrossRef] [PubMed]

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Bindewald-Wittich, A.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Birckner, E.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Bueno, J. M.

E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt. 15(2), 026007 (2010).
[CrossRef] [PubMed]

J. M. Bueno, E. J. Gualda, and P. Artal, “Adaptive optics multiphoton microscopy to study ex vivo ocular tissues,” J. Biomed. Opt. 15(6), 066004 (2010).
[CrossRef] [PubMed]

Cayouette, M.

V. Ramamurthy and M. Cayouette, “Development and disease of the photoreceptor cilium,” Clin. Genet. 76(2), 137–145 (2009).
[CrossRef] [PubMed]

Chakravarthy, U.

R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006).
[CrossRef] [PubMed]

Chance, B.

B. Chance, “Pyridine nucleotide as an indicator of the oxygen requirements for energy-linked functions of mitochondria,” Circ. Res. 38(5Suppl 1), I31–I38 (1976).
[PubMed]

Chen, C. H.

Q. Q. Wu, C. H. Chen, and Y. Koutalos, “All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion,” Biophys. J. 91(12), 4678–4689 (2006).
[CrossRef] [PubMed]

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

Chen, D. N.

L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
[CrossRef]

Chen, G.

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

Chou, C. L.

J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
[CrossRef] [PubMed]

Cornwall, M. C.

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

Cousins, S. W.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Crouch, R. K.

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

Curcio, C. A.

G. R. Jackson, C. Owsley, and C. A. Curcio, “Photoreceptor degeneration and dysfunction in aging and age-related maculopathy,” Ageing Res. Rev. 1(3), 381–396 (2002).
[CrossRef] [PubMed]

Delori, F. C.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

Dorey, C. K.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

Dubra, A.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

Dunbar, R. L.

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

Ebner, T. J.

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

Entine, G.

P. A. Liebman and G. Entine, “Visual pigments of frog and tadpole (Rana pipiens),” Vision Res. 8(7), 761–775, IN1–IN7 (1968).
[CrossRef] [PubMed]

Gao, W. C.

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

George, J. S.

X. C. Yao and J. S. George, “Near-infrared imaging of fast intrinsic optical responses in visible light-activated amphibian retina,” J. Biomed. Opt. 11(6), 064030 (2006).
[CrossRef] [PubMed]

X. C. Yao and J. S. George, “Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals,” Neuroimage 33(3), 898–906 (2006).
[CrossRef] [PubMed]

X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005).
[CrossRef] [PubMed]

Ghodasra, J. H.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Giese, G.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Goger, D. G.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

Gomi, F.

T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
[CrossRef] [PubMed]

Grieve, K.

K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008).
[CrossRef] [PubMed]

Gualda, E. J.

E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt. 15(2), 026007 (2010).
[CrossRef] [PubMed]

J. M. Bueno, E. J. Gualda, and P. Artal, “Adaptive optics multiphoton microscopy to study ex vivo ocular tissues,” J. Biomed. Opt. 15(6), 066004 (2010).
[CrossRef] [PubMed]

Hagiwara, Y.

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

Hammer, M.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Han, M.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Harwerth, R. S.

R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006).
[CrossRef] [PubMed]

Hattori, K.

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

Hebert, T.

Hillman, H.

H. Hillman, T. Hussain, and P. Sartory, “Autofluorescence of isolated unfixed rabbit Deiters’ neurons and surrounding neuroglial clamps,” Experientia 29(9), 1113–1115 (1973).
[CrossRef] [PubMed]

Hogg, R. E.

R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006).
[CrossRef] [PubMed]

Hollyfield, J. G.

A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
[PubMed]

Holz, F. G.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Hunter, J. J.

J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
[CrossRef] [PubMed]

Hussain, T.

H. Hillman, T. Hussain, and P. Sartory, “Autofluorescence of isolated unfixed rabbit Deiters’ neurons and surrounding neuroglial clamps,” Experientia 29(9), 1113–1115 (1973).
[CrossRef] [PubMed]

Hwang, J. C.

J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
[CrossRef] [PubMed]

Imanishi, Y.

Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry 46(34), 9674–9684 (2007).
[CrossRef] [PubMed]

Ito, H.

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

Jackson, G. R.

G. R. Jackson, C. Owsley, and C. A. Curcio, “Photoreceptor degeneration and dysfunction in aging and age-related maculopathy,” Ageing Res. Rev. 1(3), 381–396 (2002).
[CrossRef] [PubMed]

Jentsch, S.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Keyser, K.

Khanifar, A. A.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Kim, D. Y.

J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
[CrossRef] [PubMed]

Koutalos, Y.

Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry 46(34), 9674–9684 (2007).
[CrossRef] [PubMed]

Q. Q. Wu, C. H. Chen, and Y. Koutalos, “All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion,” Biophys. J. 91(12), 4678–4689 (2006).
[CrossRef] [PubMed]

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

La Schiazza, O.

O. La Schiazza and J. F. Bille, “High-speed two-photon excited autofluorescence imaging of ex vivo human retinal pigment epithelial cells toward age-related macular degeneration diagnostic,” J. Biomed. Opt. 13(6), 064008 (2008).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

Lederer, D. E.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Lee, J. J.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Li, Y. C.

Li, Y. G.

Liebman, P. A.

P. A. Liebman and G. Entine, “Visual pigments of frog and tadpole (Rana pipiens),” Vision Res. 8(7), 761–775, IN1–IN7 (1968).
[CrossRef] [PubMed]

Liu, L.

Lodowski, K. H.

Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry 46(34), 9674–9684 (2007).
[CrossRef] [PubMed]

Loew, L. M.

P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
[CrossRef] [PubMed]

Marmorstein, A. D.

A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
[PubMed]

Marmorstein, L. Y.

A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
[PubMed]

Merigan, W. H.

J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
[CrossRef] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

Meyer-Rüsenberg, B.

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
[CrossRef] [PubMed]

Morgan, J. I.

J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
[CrossRef] [PubMed]

Morgan, J. I. W.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

Murayama, K.

P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(03), 519–532 (1994).
[CrossRef] [PubMed]

Naarendorp, F.

P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(03), 519–532 (1994).
[CrossRef] [PubMed]

Nickells, R. W.

R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007).
[CrossRef] [PubMed]

Niemz, M. H.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

Nilsson, S. E.

S. E. Nilsson, “An electron microscopic classification of the retinal receptors of the leopard frog (Rana pipiens),” J. Ultrastruct. Res. 10(5-6), 390–416 (1964).
[CrossRef] [PubMed]

Niu, H. B.

L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
[CrossRef]

Ohgushi, H.

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

Owsley, C.

G. R. Jackson, C. Owsley, and C. A. Curcio, “Photoreceptor degeneration and dysfunction in aging and age-related maculopathy,” Ageing Res. Rev. 1(3), 381–396 (2002).
[CrossRef] [PubMed]

Pavlidis, M.

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
[CrossRef] [PubMed]

Perry, B.

Qin, Y.

Y. Qin, G. Xu, and W. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006).
[CrossRef] [PubMed]

Qu, J. L.

L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
[CrossRef]

Quigley, H. A.

R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006).
[CrossRef] [PubMed]

Ramamurthy, V.

V. Ramamurthy and M. Cayouette, “Development and disease of the photoreceptor cilium,” Clin. Genet. 76(2), 137–145 (2009).
[CrossRef] [PubMed]

Reinert, K. C.

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

Romero-Borja, F.

Roorda, A.

Sakaguchi, H.

A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
[PubMed]

Sartory, P.

H. Hillman, T. Hussain, and P. Sartory, “Autofluorescence of isolated unfixed rabbit Deiters’ neurons and surrounding neuroglial clamps,” Experientia 29(9), 1113–1115 (1973).
[CrossRef] [PubMed]

Sawa, M.

T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
[CrossRef] [PubMed]

Schenke, S.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Schmitz-Valckenberg, S.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Schweitzer, D.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Schweitzer, F.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Sieving, P. A.

P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(03), 519–532 (1994).
[CrossRef] [PubMed]

Snyder, S.

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

Snyder, S. R.

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

Staurenghi, G.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

Stinnett, S. S.

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

Strang, C.

Stupp, T.

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
[CrossRef] [PubMed]

Sun, H.

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

Thanos, S.

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
[CrossRef] [PubMed]

Tsang, S. H.

J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
[CrossRef] [PubMed]

Tsina, E.

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

Tsujikawa, M.

T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
[CrossRef] [PubMed]

Venkateswaran, K.

Vijayaraghavan, S.

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

Wakabayashi, T.

T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
[CrossRef] [PubMed]

Wang, J. Y.

Wang, W.

Y. Qin, G. Xu, and W. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006).
[CrossRef] [PubMed]

Wei, M.

P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
[CrossRef] [PubMed]

Weiter, J. J.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

Williams, D. R.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
[CrossRef] [PubMed]

Wolfe, R.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

Wu, Q. Q.

Q. Q. Wu, C. H. Chen, and Y. Koutalos, “All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion,” Biophys. J. 91(12), 4678–4689 (2006).
[CrossRef] [PubMed]

Xie, A.

P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
[CrossRef] [PubMed]

Xu, G.

Y. Qin, G. Xu, and W. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006).
[CrossRef] [PubMed]

Yamauchi, A.

Yan, P.

P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
[CrossRef] [PubMed]

Yao, X. C.

Y. G. Li, L. Liu, F. Amthor, and X. C. Yao, “High-speed line-scan confocal imaging of stimulus-evoked intrinsic optical signals in the retina,” Opt. Lett. 35(3), 426–428 (2010).
[CrossRef] [PubMed]

Y. G. Li, Q. X. Zhang, L. Liu, F. R. Amthor, and X. C. Yao, “High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation,” Opt. Express 18(7), 7210–7218 (2010).
[CrossRef] [PubMed]

Q. X. Zhang, J. Y. Wang, L. Liu, and X. C. Yao, “Microlens array recording of localized retinal responses,” Opt. Lett. 35(22), 3838–3840 (2010).
[CrossRef] [PubMed]

Y. C. Li, C. Strang, F. R. Amthor, L. Liu, Y. G. Li, Q. X. Zhang, K. Keyser, and X. C. Yao, “Parallel optical monitoring of visual signal propagation from the photoreceptors to the inner retina layers,” Opt. Lett. 35(11), 1810–1812 (2010).
[CrossRef] [PubMed]

X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008).
[CrossRef] [PubMed]

Y. B. Zhao and X. C. Yao, “Intrinsic optical imaging of stimulus-modulated physiological responses in amphibian retina,” Opt. Lett. 33(4), 342–344 (2008).
[CrossRef] [PubMed]

X. C. Yao and J. S. George, “Near-infrared imaging of fast intrinsic optical responses in visible light-activated amphibian retina,” J. Biomed. Opt. 11(6), 064030 (2006).
[CrossRef] [PubMed]

X. C. Yao and J. S. George, “Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals,” Neuroimage 33(3), 898–906 (2006).
[CrossRef] [PubMed]

X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005).
[CrossRef] [PubMed]

Yu, J. Y.

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

Zhang, Q. X.

Zhao, L. L.

L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
[CrossRef]

Zhao, Y. B.

Acta Ophthalmol. (Copenh.)

T. Wakabayashi, M. Sawa, F. Gomi, and M. Tsujikawa, “Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa,” Acta Ophthalmol. (Copenh.) 88(5), e177–e183 (2010).
[CrossRef] [PubMed]

Ageing Res. Rev.

G. R. Jackson, C. Owsley, and C. A. Curcio, “Photoreceptor degeneration and dysfunction in aging and age-related maculopathy,” Ageing Res. Rev. 1(3), 381–396 (2002).
[CrossRef] [PubMed]

Appl. Opt.

Arch. Ophthalmol.

R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006).
[CrossRef] [PubMed]

Biochemistry

Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry 46(34), 9674–9684 (2007).
[CrossRef] [PubMed]

Biophys. J.

C. H. Chen, E. Tsina, M. C. Cornwall, R. K. Crouch, S. Vijayaraghavan, and Y. Koutalos, “Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors,” Biophys. J. 88(3), 2278–2287 (2005).
[CrossRef] [PubMed]

Q. Q. Wu, C. H. Chen, and Y. Koutalos, “All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion,” Biophys. J. 91(12), 4678–4689 (2006).
[CrossRef] [PubMed]

Circ. Res.

B. Chance, “Pyridine nucleotide as an indicator of the oxygen requirements for energy-linked functions of mitochondria,” Circ. Res. 38(5Suppl 1), I31–I38 (1976).
[PubMed]

Clin. Genet.

V. Ramamurthy and M. Cayouette, “Development and disease of the photoreceptor cilium,” Clin. Genet. 76(2), 137–145 (2009).
[CrossRef] [PubMed]

Curr. Eye Res.

Y. Qin, G. Xu, and W. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006).
[CrossRef] [PubMed]

Experientia

H. Hillman, T. Hussain, and P. Sartory, “Autofluorescence of isolated unfixed rabbit Deiters’ neurons and surrounding neuroglial clamps,” Experientia 29(9), 1113–1115 (1973).
[CrossRef] [PubMed]

Graefes Arch. Clin. Exp. Ophthalmol.

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci.

A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, and J. G. Hollyfield, “Spectral profiling of autofluorescence associated with lipofuscin, Bruch’s Membrane, and sub-RPE deposits in normal and AMD eyes,” Invest. Ophthalmol. Vis. Sci. 43(7), 2435–2441 (2002).
[PubMed]

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995).
[PubMed]

A. Bindewald-Wittich, M. Han, S. Schmitz-Valckenberg, S. R. Snyder, G. Giese, J. F. Bille, and F. G. Holz, “Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:sapphire laser,” Invest. Ophthalmol. Vis. Sci. 47(10), 4553–4557 (2006).
[CrossRef] [PubMed]

J. I. Morgan, J. J. Hunter, W. H. Merigan, and D. R. Williams, “The reduction of retinal autofluorescence caused by light exposure,” Invest. Ophthalmol. Vis. Sci. 50(12), 6015–6022 (2009).
[CrossRef] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[CrossRef] [PubMed]

K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008).
[CrossRef] [PubMed]

J. Biomed. Opt.

X. C. Yao and J. S. George, “Near-infrared imaging of fast intrinsic optical responses in visible light-activated amphibian retina,” J. Biomed. Opt. 11(6), 064030 (2006).
[CrossRef] [PubMed]

M. Han, A. Bindewald-Wittich, F. G. Holz, G. Giese, M. H. Niemz, S. Snyder, H. Sun, J. Y. Yu, M. Agopov, O. La Schiazza, and J. F. Bille, “Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells,” J. Biomed. Opt. 11(1), 010501 (2006).
[CrossRef] [PubMed]

M. Han, G. Giese, S. Schmitz-Valckenberg, A. Bindewald-Wittich, F. G. Holz, J. Y. Yu, J. F. Bille, and M. H. Niemz, “Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging,” J. Biomed. Opt. 12(2), 024012 (2007).
[CrossRef] [PubMed]

J. M. Bueno, E. J. Gualda, and P. Artal, “Adaptive optics multiphoton microscopy to study ex vivo ocular tissues,” J. Biomed. Opt. 15(6), 066004 (2010).
[CrossRef] [PubMed]

E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt. 15(2), 026007 (2010).
[CrossRef] [PubMed]

O. La Schiazza and J. F. Bille, “High-speed two-photon excited autofluorescence imaging of ex vivo human retinal pigment epithelial cells toward age-related macular degeneration diagnostic,” J. Biomed. Opt. 13(6), 064008 (2008).
[CrossRef] [PubMed]

J. Biomed. Sci. Eng.

L. L. Zhao, J. L. Qu, D. N. Chen, and H. B. Niu, “Layered-resolved autofluorescence imaging of photoreceptors using two-photon excitation,” J. Biomed. Sci. Eng. 02(05), 363–365 (2009).
[CrossRef]

J. Neurophysiol.

K. C. Reinert, R. L. Dunbar, W. C. Gao, G. Chen, and T. J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92(1), 199–211 (2004).
[CrossRef] [PubMed]

J. Org. Chem.

P. Yan, A. Xie, M. Wei, and L. M. Loew, “Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores,” J. Org. Chem. 73(17), 6587–6594 (2008).
[CrossRef] [PubMed]

J. Tissue Eng. Regen. Med.

Y. Hagiwara, K. Hattori, T. Aoki, H. Ohgushi, and H. Ito, “Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser,” J. Tissue Eng. Regen. Med. 5(2), 163–168 (2011).
[CrossRef] [PubMed]

J. Ultrastruct. Res.

S. E. Nilsson, “An electron microscopic classification of the retinal receptors of the leopard frog (Rana pipiens),” J. Ultrastruct. Res. 10(5-6), 390–416 (1964).
[CrossRef] [PubMed]

Microsc. Res. Tech.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[CrossRef] [PubMed]

Neuroimage

X. C. Yao and J. S. George, “Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals,” Neuroimage 33(3), 898–906 (2006).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Prog. Retin. Eye Res.

R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006).
[CrossRef] [PubMed]

Retina

S. Bearelly, A. A. Khanifar, D. E. Lederer, J. J. Lee, J. H. Ghodasra, S. S. Stinnett, and S. W. Cousins, “Use of fundus autofluorescence images to predict geographic atrophy progression,” Retina 31(1), 81–86 (2011).
[CrossRef] [PubMed]

J. C. Hwang, D. Y. Kim, C. L. Chou, and S. H. Tsang, “Fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis,” Retina 30(7), 1095–1103 (2010).
[CrossRef] [PubMed]

Vet. Ophthalmol.

R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007).
[CrossRef] [PubMed]

Vis. Neurosci.

P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(03), 519–532 (1994).
[CrossRef] [PubMed]

Vision Res.

P. A. Liebman and G. Entine, “Visual pigments of frog and tadpole (Rana pipiens),” Vision Res. 8(7), 761–775, IN1–IN7 (1968).
[CrossRef] [PubMed]

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (6)

Fig. 1
Fig. 1

Schematic diagram of the experimental setup for two-photon imaging of the frog retina. A mode-locked Ti:sapphire laser (Chameleon, Coherent Inc.) was used to provide excitation light (720 nm). At the dichroic mirror, the long-wavelength 720 nm excitation light (red rays) was passed through and the short-wavelength emission light (green rays) was reflected. A band-pass (450-550 nm) filter was placed in front of the photomultiplier tube (PMT).

Fig. 2
Fig. 2

(A) Transmission image of a frog retinal slice. During the recording, the retinal slice was continuously illuminated by an infrared (800-1000 nm) light. The PRL, ONL, OPL, INL, IPL, GCL could be directly differentiated. (B) Representative two-photon fluorescence image of frog retinal slices. The excitation light was set at 720 nm, and the average power is ~5 mW. In this image, single cellular structures (green arrowheads) were clearly observed in the PRL, ONL, INL, and GCL. Individual Müller glial cells (red arrowheads) were observed. (C) Averaged autofluorescence (AF) signal at each depth of the retinal slice shown in Fig. 2B.

Fig. 3
Fig. 3

Two-photon excited autofluorescence imaging of the flat-mounted retina. The 720 nm excitation light was delivered from the GCL side, i.e., the GCL side faced to the objective in Fig. 1. Two-photon images of the PRL (A), ONL (B), OPL (C), INL (D), IPL (E), and GCL (F), were collected with identical excitation power of ~10 mW. The white square in A marks the region of interest shown in greater detail in Fig. 4. (G) Depth-resolved scan, i.e., a cross-section, of a line area of the flat-mounted retina. (H) Comparison of rod and cone autofluorescence recorded from 6 retinal preparations R1-6. For each retina, 10 rods and 10 cones were randomly selected for average calculations of the rod and cone autofluorescence. The line bars indicate standard deviation.

Fig. 4
Fig. 4

(A) Enlarged PRL illustration of a sub-image marked by the white square in Fig. 3A. This image revealed that the rod (blue arrowheads) autofluorescence was relatively homogenous at the cellular level; while a bright spot with sub-cellular structure was frequently observed in the cones (red arrowheads). (B) Another example of autofluorescence image of the rod and cone mosaics. Bright autofluorescence spots were consistently observed in the cones (red arrowheads) and double cones (green arrowhead). (C) and (D) show peak and average values of 5 representative cones and 5 rods, respectively.

Fig. 5
Fig. 5

Top panel shows depth-resolved imaging of the PRL autofluorescence. The images were collected with 2 μm depth interval and 0.3 μm pixel size. The excitation power was ~5 mW. A bright autofluorescence spot was frequently observed in the cone. Primary bright spots were localized at z = 16-30 μm relative to the PRL side retinal surface. Bottom panel is quantitative comparison of autofluorescence between rods and cones at z = 12-34 μm. At each depth, 6 rods and 6 cones were used for averaging. The line bars indicate standard deviation.

Fig. 6
Fig. 6

Averaged autofluorescence of the PRL, ONL, OPL, INL, IPL and GCL. 6 retinal slices and 6 flat-mounted retinas were used for the average. Red and blue bars show the signals recorded from retinal slices and flat-mounted retinas, respectively. The line bars indicate standard deviation.

Metrics