Abstract

Retinal image quality from flood illumination adaptive optics (AO) ophthalmoscopes is adversely affected by out-of-focus light scatter due to the lack of confocality. This effect is more pronounced in small eyes, such as that of rodents, because the requisite high optical power confers a large dioptric thickness to the retina. A recently-developed structured illumination microscopy (SIM) technique called HiLo imaging has been shown to reduce the effect of out-of-focus light scatter in flood illumination microscopes and produce pseudo-confocal images with significantly improved image quality. In this work, we adopted the HiLo technique to a flood AO ophthalmoscope and performed AO imaging in both (physical) model and live rat eyes. The improvement in image quality from HiLo imaging is shown both qualitatively and quantitatively by using spatial spectral analysis.

© 2014 Optical Society of America

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  1. B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
    [Crossref] [PubMed]
  2. B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
    [Crossref] [PubMed]
  3. K. Kohzaki, A. J. Vingrys, and B. V. Bui, “Early inner retinal dysfunction in streptozotocin-induced diabetic rats,” Invest. Ophthalmol. Vis. Sci. 49(8), 3595–3604 (2008).
    [Crossref] [PubMed]
  4. Z. He, B. V. Bui, and A. J. Vingrys, “Effect of repeated iop challenge on rat retinal function,” Invest. Ophthalmol. Vis. Sci. 49(7), 3026–3034 (2008).
    [Crossref] [PubMed]
  5. R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
    [PubMed]
  6. S. L. Mansour, K. R. Thomas, and M. R. Capecchi, “Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes,” Nature 336(6197), 348–352 (1988).
    [Crossref] [PubMed]
  7. M. R. Capecchi, “Altering the genome by homologous recombination,” Science 244(4910), 1288–1292 (1989).
    [Crossref] [PubMed]
  8. A. Abbott, “Laboratory animals: The renaissance rat,” Nature 428(6982), 464–466 (2004).
    [Crossref] [PubMed]
  9. A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
    [Crossref] [PubMed]
  10. X. Zhou, P. Bedggood, and A. Metha, “Limitations to adaptive optics image quality in rodent eyes,” Biomed. Opt. Express 3(8), 1811–1824 (2012).
    [Crossref] [PubMed]
  11. Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
    [Crossref] [PubMed]
  12. Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
    [Crossref] [PubMed]
  13. J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
    [Crossref] [PubMed]
  14. A. Roorda, F. Romero-Borja, W. Donnelly, H. Queener, T. Hebert, and M. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10(9), 405–412 (2002).
    [Crossref] [PubMed]
  15. R. J. Zawadzki, S. S. Choi, S. M. Jones, S. S. Oliver, and J. S. Werner, “Adaptive optics-optical coherence tomography: Optimizing visualization of microscopic retinal structures in three dimensions,” J. Opt. Soc. Am. A 24(5), 1373–1383 (2007).
    [Crossref] [PubMed]
  16. M. Pircher, R. J. Zawadzki, J. W. Evans, J. S. Werner, and C. K. Hitzenberger, “Simultaneous imaging of human cone mosaic with adaptive optics enhanced scanning laser ophthalmoscopy and high-speed transversal scanning optical coherence tomography,” Opt. Lett. 33(1), 22–24 (2008).
    [Crossref] [PubMed]
  17. Y. F. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt. 18(5), 056007 (2013).
    [Crossref] [PubMed]
  18. A. Roorda, “Applications of adaptive optics scanning laser ophthalmoscopy,” Optom. Vis. Sci. 87(4), 260–268 (2010).
    [PubMed]
  19. J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2(4), 781–793 (2011).
    [Crossref] [PubMed]
  20. P. Bedggood and A. Metha, “Analysis of contrast and motion signals generated by human blood constituents in capillary flow,” Opt. Lett. 39(3), 610–613 (2014).
    [Crossref] [PubMed]
  21. P. Bedggood and A. Metha, “Optical imaging of human cone photoreceptors directly following the capture of light,” PLoS ONE 8(11), e79251 (2013).
    [Crossref] [PubMed]
  22. P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express 3(12), 3264–3277 (2012).
    [Crossref] [PubMed]
  23. D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33(16), 1819–1821 (2008).
    [Crossref] [PubMed]
  24. D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination hilo microscopy,” J. Biomed. Opt. 16(1), 016014 (2011).
    [Crossref] [PubMed]
  25. S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
    [Crossref] [PubMed]
  26. C. A. Schneider, W. S. Rasband, and K. W. Eliceiri, “Nih image to imagej: 25 years of image analysis,” Nat. Methods 9(7), 671–675 (2012).
    [Crossref] [PubMed]
  27. D. Lim and J. Mertz, “Hilo imagej plugin (version 1.2),” (2013), http://biomicroscopy.bu.edu/resources/ .
  28. T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
    [Crossref] [PubMed]
  29. J. Liang and D. R. Williams, “Aberrations and retinal image quality of the normal human eye,” J. Opt. Soc. Am. A 14(11), 2873–2883 (1997).
    [Crossref] [PubMed]
  30. A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(6), 1757–1768 (2011).
    [Crossref] [PubMed]
  31. J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
    [Crossref] [PubMed]
  32. Y. Geng, L. A. Schery, R. Sharma, A. Dubra, K. Ahmad, R. T. Libby, and D. R. Williams, “Optical properties of the mouse eye,” Biomed. Opt. Express 2(4), 717–738 (2011).
    [Crossref] [PubMed]
  33. A. Hughes, “A schematic eye for the rat,” Vision Res. 19(5), 569–588 (1979).
    [Crossref] [PubMed]
  34. F. C. Delori, R. H. Webb, D. H. Sliney, and American National Standards Institute, “Maximum permissible exposures for ocular safety (ansi 2000), with emphasis on ophthalmic devices,” J. Opt. Soc. Am. A 24(5), 1250–1265 (2007).
    [Crossref] [PubMed]
  35. Y. N. Sulai and A. Dubra, “Optical design of a broadband scanning adaptive optics ophthalmoscope for the mouse eye,” in SPIE Proceedings(MEMS Adaptive Optics VIII, 2014), pp. 89780E–89780E–89789.
  36. J. Michaelson, H. J. Choi, P. So, and H. D. Huang, “Depth-resolved cellular microrheology using hilo microscopy,” Biomed. Opt. Express 3(6), 1241–1255 (2012).
    [Crossref] [PubMed]
  37. A. Pinhas, M. Dubow, N. Shah, T. Y. Chui, D. Scoles, Y. N. Sulai, R. Weitz, J. B. Walsh, J. Carroll, A. Dubra, and R. B. Rosen, “In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Biomed. Opt. Express 4(8), 1305–1317 (2013).
    [Crossref] [PubMed]
  38. H. Hofer, N. Sredar, H. Queener, C. Li, and J. Porter, “Wavefront sensorless adaptive optics ophthalmoscopy in the human eye,” Opt. Express 19(15), 14160–14171 (2011).
    [Crossref] [PubMed]
  39. Y. Jian, J. Xu, M. A. Gradowski, S. Bonora, R. J. Zawadzki, and M. V. Sarunic, “Wavefront sensorless adaptive optics optical coherence tomography for in vivo retinal imaging in mice,” Biomed. Opt. Express 5(2), 547–559 (2014).
    [Crossref] [PubMed]

2014 (2)

2013 (4)

P. Bedggood and A. Metha, “Optical imaging of human cone photoreceptors directly following the capture of light,” PLoS ONE 8(11), e79251 (2013).
[Crossref] [PubMed]

A. Pinhas, M. Dubow, N. Shah, T. Y. Chui, D. Scoles, Y. N. Sulai, R. Weitz, J. B. Walsh, J. Carroll, A. Dubra, and R. B. Rosen, “In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Biomed. Opt. Express 4(8), 1305–1317 (2013).
[Crossref] [PubMed]

J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

Y. F. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt. 18(5), 056007 (2013).
[Crossref] [PubMed]

2012 (6)

2011 (5)

2010 (2)

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
[Crossref] [PubMed]

A. Roorda, “Applications of adaptive optics scanning laser ophthalmoscopy,” Optom. Vis. Sci. 87(4), 260–268 (2010).
[PubMed]

2009 (4)

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

2008 (5)

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33(16), 1819–1821 (2008).
[Crossref] [PubMed]

K. Kohzaki, A. J. Vingrys, and B. V. Bui, “Early inner retinal dysfunction in streptozotocin-induced diabetic rats,” Invest. Ophthalmol. Vis. Sci. 49(8), 3595–3604 (2008).
[Crossref] [PubMed]

Z. He, B. V. Bui, and A. J. Vingrys, “Effect of repeated iop challenge on rat retinal function,” Invest. Ophthalmol. Vis. Sci. 49(7), 3026–3034 (2008).
[Crossref] [PubMed]

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

M. Pircher, R. J. Zawadzki, J. W. Evans, J. S. Werner, and C. K. Hitzenberger, “Simultaneous imaging of human cone mosaic with adaptive optics enhanced scanning laser ophthalmoscopy and high-speed transversal scanning optical coherence tomography,” Opt. Lett. 33(1), 22–24 (2008).
[Crossref] [PubMed]

2007 (2)

2005 (1)

B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
[Crossref] [PubMed]

2004 (1)

A. Abbott, “Laboratory animals: The renaissance rat,” Nature 428(6982), 464–466 (2004).
[Crossref] [PubMed]

2002 (1)

1997 (1)

1989 (1)

M. R. Capecchi, “Altering the genome by homologous recombination,” Science 244(4910), 1288–1292 (1989).
[Crossref] [PubMed]

1988 (1)

S. L. Mansour, K. R. Thomas, and M. R. Capecchi, “Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes,” Nature 336(6197), 348–352 (1988).
[Crossref] [PubMed]

1979 (1)

A. Hughes, “A schematic eye for the rat,” Vision Res. 19(5), 569–588 (1979).
[Crossref] [PubMed]

Abbott, A.

A. Abbott, “Laboratory animals: The renaissance rat,” Nature 428(6982), 464–466 (2004).
[Crossref] [PubMed]

Ahmad, K.

Anegon, I.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Bartoo, A. C.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Bedggood, P.

Bonora, S.

Bozinovic, N.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Buelow, R.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Bui, B. V.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

K. Kohzaki, A. J. Vingrys, and B. V. Bui, “Early inner retinal dysfunction in streptozotocin-induced diabetic rats,” Invest. Ophthalmol. Vis. Sci. 49(8), 3595–3604 (2008).
[Crossref] [PubMed]

Z. He, B. V. Bui, and A. J. Vingrys, “Effect of repeated iop challenge on rat retinal function,” Invest. Ophthalmol. Vis. Sci. 49(7), 3026–3034 (2008).
[Crossref] [PubMed]

B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
[Crossref] [PubMed]

Campbell, M.

Capecchi, M. R.

M. R. Capecchi, “Altering the genome by homologous recombination,” Science 244(4910), 1288–1292 (1989).
[Crossref] [PubMed]

S. L. Mansour, K. R. Thomas, and M. R. Capecchi, “Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes,” Nature 336(6197), 348–352 (1988).
[Crossref] [PubMed]

Carroll, J.

Choi, H. J.

Choi, S. S.

Choi, V. M.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Chu, K. K.

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination hilo microscopy,” J. Biomed. Opt. 16(1), 016014 (2011).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33(16), 1819–1821 (2008).
[Crossref] [PubMed]

Chui, T. Y.

Cioffi, G. A.

B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
[Crossref] [PubMed]

Cost, G. J.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Cui, X.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Davis, G. D.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Delori, F. C.

Donnelly, W.

Dubow, M.

Dubra, A.

Edmunds, B.

B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
[Crossref] [PubMed]

Eliceiri, K. W.

C. A. Schneider, W. S. Rasband, and K. W. Eliceiri, “Nih image to imagej: 25 years of image analysis,” Nat. Methods 9(7), 671–675 (2012).
[Crossref] [PubMed]

Evans, J. W.

Flannery, J. G.

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Foeckler, J.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Ford, T. N.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination hilo microscopy,” J. Biomed. Opt. 16(1), 016014 (2011).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Fortune, B.

B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
[Crossref] [PubMed]

Freyvert, Y.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Geng, Y.

J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
[Crossref] [PubMed]

Y. Geng, L. A. Schery, R. Sharma, A. Dubra, K. Ahmad, R. T. Libby, and D. R. Williams, “Optical properties of the mouse eye,” Biomed. Opt. Express 2(4), 717–738 (2011).
[Crossref] [PubMed]

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Geurts, A. M.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Gradowski, M. A.

Gray, D. C.

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Greenberg, K. P.

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Gregory, P. D.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

He, Z.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Z. He, B. V. Bui, and A. J. Vingrys, “Effect of repeated iop challenge on rat retinal function,” Invest. Ophthalmol. Vis. Sci. 49(7), 3026–3034 (2008).
[Crossref] [PubMed]

Hebert, T.

Hitzenberger, C. K.

Hofer, H.

Hourtoule, C.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Huang, H. D.

Hughes, A.

A. Hughes, “A schematic eye for the rat,” Vision Res. 19(5), 569–588 (1979).
[Crossref] [PubMed]

Hunter, J. J.

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Jacob, H. J.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Jenkins, S. S.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Jian, Y.

Jian, Y. F.

Y. F. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt. 18(5), 056007 (2013).
[Crossref] [PubMed]

Jones, B. W.

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Jones, S. M.

Kalloway, S.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Kohzaki, K.

K. Kohzaki, A. J. Vingrys, and B. V. Bui, “Early inner retinal dysfunction in streptozotocin-induced diabetic rats,” Invest. Ophthalmol. Vis. Sci. 49(8), 3595–3604 (2008).
[Crossref] [PubMed]

Lam, S.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Li, C.

Liang, J.

Libby, R. T.

Lim, D.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination hilo microscopy,” J. Biomed. Opt. 16(1), 016014 (2011).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33(16), 1819–1821 (2008).
[Crossref] [PubMed]

Loeliger, M.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Mansour, S. L.

S. L. Mansour, K. R. Thomas, and M. R. Capecchi, “Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes,” Nature 336(6197), 348–352 (1988).
[Crossref] [PubMed]

Marc, R. E.

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Martin, J. A.

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
[Crossref] [PubMed]

Meng, X.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Ménoret, S.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Merigan, W. H.

Mertz, J.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination hilo microscopy,” J. Biomed. Opt. 16(1), 016014 (2011).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett. 33(16), 1819–1821 (2008).
[Crossref] [PubMed]

Metha, A.

Michaelson, J.

Michalkiewicz, M.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Miller, J. C.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Nguyen, C. T.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Nguyen, H.

J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

Oliver, S. S.

Organisciak, D. T.

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Pinhas, A.

Pircher, M.

Porter, J.

H. Hofer, N. Sredar, H. Queener, C. Li, and J. Porter, “Wavefront sensorless adaptive optics ophthalmoscopy in the human eye,” Opt. Express 19(15), 14160–14171 (2011).
[Crossref] [PubMed]

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Queener, H.

Rasband, W. S.

C. A. Schneider, W. S. Rasband, and K. W. Eliceiri, “Nih image to imagej: 25 years of image analysis,” Nat. Methods 9(7), 671–675 (2012).
[Crossref] [PubMed]

Rebar, E. J.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Rees, S. M.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Romero-Borja, F.

Roorda, A.

Rosen, R. B.

Santos, S.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Sarunic, M. V.

Schallek, J. B.

J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

Schery, L. A.

Schilling, R.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Schneider, C. A.

C. A. Schneider, W. S. Rasband, and K. W. Eliceiri, “Nih image to imagej: 25 years of image analysis,” Nat. Methods 9(7), 671–675 (2012).
[Crossref] [PubMed]

Scoles, D.

Shah, N.

Sharma, R.

Singh, S. K.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Sliney, D. H.

So, P.

Sredar, N.

Sulai, Y.

Sulai, Y. N.

Tam, J.

Thomas, K. R.

S. L. Mansour, K. R. Thomas, and M. R. Capecchi, “Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes,” Nature 336(6197), 348–352 (1988).
[Crossref] [PubMed]

Thomas, M.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Tiruveedhula, P.

Tolcos, M.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Urnov, F. D.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Vaughan, D. K.

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Vazquez-Chona, F.

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Vincent, A.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Vingrys, A. J.

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

K. Kohzaki, A. J. Vingrys, and B. V. Bui, “Early inner retinal dysfunction in streptozotocin-induced diabetic rats,” Invest. Ophthalmol. Vis. Sci. 49(8), 3595–3604 (2008).
[Crossref] [PubMed]

Z. He, B. V. Bui, and A. J. Vingrys, “Effect of repeated iop challenge on rat retinal function,” Invest. Ophthalmol. Vis. Sci. 49(7), 3026–3034 (2008).
[Crossref] [PubMed]

Walsh, J. B.

Watt, C. B.

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Webb, R. H.

Weiler, H.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Weitz, R.

Werner, J. S.

Williams, D. R.

J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
[Crossref] [PubMed]

Y. Geng, L. A. Schery, R. Sharma, A. Dubra, K. Ahmad, R. T. Libby, and D. R. Williams, “Optical properties of the mouse eye,” Biomed. Opt. Express 2(4), 717–738 (2011).
[Crossref] [PubMed]

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

J. Liang and D. R. Williams, “Aberrations and retinal image quality of the normal human eye,” J. Opt. Soc. Am. A 14(11), 2873–2883 (1997).
[Crossref] [PubMed]

Wolfe, R.

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

Wood, A.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Xu, J.

Yin, L.

Zawadzki, R. J.

Zeitler, B.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Zhang, L.

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

Zhou, X.

Biomed. Opt. Express (9)

X. Zhou, P. Bedggood, and A. Metha, “Limitations to adaptive optics image quality in rodent eyes,” Biomed. Opt. Express 3(8), 1811–1824 (2012).
[Crossref] [PubMed]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
[Crossref] [PubMed]

J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2(4), 781–793 (2011).
[Crossref] [PubMed]

P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express 3(12), 3264–3277 (2012).
[Crossref] [PubMed]

A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(6), 1757–1768 (2011).
[Crossref] [PubMed]

Y. Geng, L. A. Schery, R. Sharma, A. Dubra, K. Ahmad, R. T. Libby, and D. R. Williams, “Optical properties of the mouse eye,” Biomed. Opt. Express 2(4), 717–738 (2011).
[Crossref] [PubMed]

J. Michaelson, H. J. Choi, P. So, and H. D. Huang, “Depth-resolved cellular microrheology using hilo microscopy,” Biomed. Opt. Express 3(6), 1241–1255 (2012).
[Crossref] [PubMed]

A. Pinhas, M. Dubow, N. Shah, T. Y. Chui, D. Scoles, Y. N. Sulai, R. Weitz, J. B. Walsh, J. Carroll, A. Dubra, and R. B. Rosen, “In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Biomed. Opt. Express 4(8), 1305–1317 (2013).
[Crossref] [PubMed]

Y. Jian, J. Xu, M. A. Gradowski, S. Bonora, R. J. Zawadzki, and M. V. Sarunic, “Wavefront sensorless adaptive optics optical coherence tomography for in vivo retinal imaging in mice,” Biomed. Opt. Express 5(2), 547–559 (2014).
[Crossref] [PubMed]

Exp. Eye Res. (1)

B. V. Bui, M. Loeliger, M. Thomas, A. J. Vingrys, S. M. Rees, C. T. Nguyen, Z. He, and M. Tolcos, “Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats,” Exp. Eye Res. 88(6), 1076–1083 (2009).
[Crossref] [PubMed]

Invest. Ophthalmol. Vis. Sci. (6)

K. Kohzaki, A. J. Vingrys, and B. V. Bui, “Early inner retinal dysfunction in streptozotocin-induced diabetic rats,” Invest. Ophthalmol. Vis. Sci. 49(8), 3595–3604 (2008).
[Crossref] [PubMed]

Z. He, B. V. Bui, and A. J. Vingrys, “Effect of repeated iop challenge on rat retinal function,” Invest. Ophthalmol. Vis. Sci. 49(7), 3026–3034 (2008).
[Crossref] [PubMed]

Y. Geng, K. P. Greenberg, R. Wolfe, D. C. Gray, J. J. Hunter, A. Dubra, J. G. Flannery, D. R. Williams, and J. Porter, “In vivo imaging of microscopic structures in the rat retina,” Invest. Ophthalmol. Vis. Sci. 50(12), 5872–5879 (2009).
[Crossref] [PubMed]

J. B. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
[Crossref] [PubMed]

B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune, “The gradient of retinal functional changes during acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 46(1), 202–213 (2005).
[Crossref] [PubMed]

J. Biomed. Opt. (4)

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence hilo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[Crossref] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination hilo microscopy,” J. Biomed. Opt. 16(1), 016014 (2011).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14(3), 030502 (2009).
[Crossref] [PubMed]

Y. F. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt. 18(5), 056007 (2013).
[Crossref] [PubMed]

J. Opt. Soc. Am. A (3)

Mol. Vis. (1)

R. E. Marc, B. W. Jones, C. B. Watt, F. Vazquez-Chona, D. K. Vaughan, and D. T. Organisciak, “Extreme retinal remodeling triggered by light damage: Implications for age related macular degeneration,” Mol. Vis. 14, 782–806 (2008).
[PubMed]

Nat. Methods (1)

C. A. Schneider, W. S. Rasband, and K. W. Eliceiri, “Nih image to imagej: 25 years of image analysis,” Nat. Methods 9(7), 671–675 (2012).
[Crossref] [PubMed]

Nature (2)

S. L. Mansour, K. R. Thomas, and M. R. Capecchi, “Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes,” Nature 336(6197), 348–352 (1988).
[Crossref] [PubMed]

A. Abbott, “Laboratory animals: The renaissance rat,” Nature 428(6982), 464–466 (2004).
[Crossref] [PubMed]

Opt. Express (2)

Opt. Lett. (3)

Optom. Vis. Sci. (1)

A. Roorda, “Applications of adaptive optics scanning laser ophthalmoscopy,” Optom. Vis. Sci. 87(4), 260–268 (2010).
[PubMed]

PLoS ONE (1)

P. Bedggood and A. Metha, “Optical imaging of human cone photoreceptors directly following the capture of light,” PLoS ONE 8(11), e79251 (2013).
[Crossref] [PubMed]

Science (2)

A. M. Geurts, G. J. Cost, Y. Freyvert, B. Zeitler, J. C. Miller, V. M. Choi, S. S. Jenkins, A. Wood, X. Cui, X. Meng, A. Vincent, S. Lam, M. Michalkiewicz, R. Schilling, J. Foeckler, S. Kalloway, H. Weiler, S. Ménoret, I. Anegon, G. D. Davis, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, H. J. Jacob, and R. Buelow, “Knockout rats via embryo microinjection of zinc-finger nucleases,” Science 325(5939), 433 (2009).
[Crossref] [PubMed]

M. R. Capecchi, “Altering the genome by homologous recombination,” Science 244(4910), 1288–1292 (1989).
[Crossref] [PubMed]

Vision Res. (1)

A. Hughes, “A schematic eye for the rat,” Vision Res. 19(5), 569–588 (1979).
[Crossref] [PubMed]

Other (2)

Y. N. Sulai and A. Dubra, “Optical design of a broadband scanning adaptive optics ophthalmoscope for the mouse eye,” in SPIE Proceedings(MEMS Adaptive Optics VIII, 2014), pp. 89780E–89780E–89789.

D. Lim and J. Mertz, “Hilo imagej plugin (version 1.2),” (2013), http://biomicroscopy.bu.edu/resources/ .

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Figures (9)

Fig. 1
Fig. 1

Scaled (1:1) schematic layout of our non-planar design flood-illumination AO ophthalmoscope, flattened for visualization. All angles and distances are to scale. Representations of optical components are for illustrative purposes only. Two illumination arms are built in: the “wide-field illumination arm” and the “AO illumination arm”. The two arms can be switched by using the three flip mirrors marked with an asterisk (*FM). DPSS: diode-pumped solid-state laser. SPR: spatial phase randomizer. M: flat mirrors. BS: plate beam splitter. FM: flip mirrors. CM: curved mirrors. P: pupil planes conjugate to the wavefront sensor and deformable mirror. DM: Mirao 52d deformable mirror. WFS: wavefront sensor. Note that SPR1 (coupled to imaging light) was switched on and off for HiLo imaging (see description below), and SPR2 (coupled to wavefront sensing light) was left on throughout the experiment. Scale bar: 100 mm.

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Fig. 2
Fig. 2

In vivo image of a human eye using our rat AO system. Image is located approximately 2° superior from fixation, averaged over 30 frames and linearly stretched to fill the colormap for display purposes. Cones are clearly visible at the centre of the image. The fovea is towards the bottom. Scale bar = 30 µm.

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Fig. 3
Fig. 3

Example of AO images obtained using the 60 D model eye with an artificial “retina” made from a white piece of paper printed with ink spots, together with an intraocular scatterer. All images shown are the average of 50 frames and linearly stretched to fill the colormap for display purposes. Uniform (a) and Speckle (b) images were obtained with the scatterer in place and with uniform and speckle illumination, respectively. HiLo images were generated using two different values for the depth-of-field (DOF), with DOFx4 in (c) and DOFx8 in (d), with the circled areas showing greater enhancement of higher frequency details for the DOFx4 HiLo image in (c), and greater enhancement of lower frequency details for the DOFx8 HiLo image in (d) (see Fig. 4 for Fourier analysis). The Ideal image (e), which was obtained without the scatterer, is also shown for comparison. Scale bar = 50 µm.

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Fig. 4
Fig. 4

Analysis showing improvement to the retinal image power spectrum following HiLo (with scatterer), compared to that obtained after physical removal of the scatterer (Ideal image) for the 60 D model eye. TOP CENTRE: Ratio plot of the normalized radial average energy of the FFT power spectrum of the images shown in Fig. 3. All results are normalized by the Uniform image power spectrum, represented by a horizontal dash-dot line at ratio = 1.0. The horizontal axis represents spatial frequency in units of cycles/mm. INSET TOP LEFT: Magnified view at lower spatial frequencies. Low frequency information occupies a lower fraction of the energy spectrum after HiLo, due to removal of veiling glare introduced by the scatterer. Performance approaches that of the ideal image. An example low frequency retinal feature (~4 cycles/mm) is highlighted in the Ideal image at BOTTOM. INSET TOP RIGHT: Magnified view of the higher spatial frequencies. High frequency information occupies a greater fraction of the energy spectrum after HiLo, due to removal of the low frequency veiling glare. An example high frequency retinal feature (~70 cycles/mm) is highlighted at BOTTOM.

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Fig. 5
Fig. 5

Uniform and HiLo images obtained from the 220 D model eye, using a 45 µm thick lens cleaning tissue as the artificial retina. All images shown are the average of 50 frames and stretched to fill the colormap for display purposes. (a) and (c): Uniform and HiLo images for the most anterior surface of the cleaning tissue. It can be seen that light scatter from posterior layers is reduced greatly in the HiLo image. (b) and (d): Uniform and HiLo images for the most posterior surface. Scale bar = 20 µm.

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Fig. 6
Fig. 6

An example of the Shack-Hartmann WFS spot quality from the rat eye prior to AO correction after optimization and, following adoption of the system modifications suggested by Geng et al. (2011) [32] summarized in the text. The spots appear well focussed at the centre, but become gradually blurry towards the periphery. The RMS wavefront error from the rat eye following adaptive optics correction ranged from 0.06 to 0.10 µm, measured over a 3.75 mm pupil.

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Fig. 7
Fig. 7

Example of in vivo AO retinal images obtained from Long Evans rat #1, showing a large blood vessel. All images shown are the average of 80 frames and linearly stretched for display purposes. Uniform, Speckle and Hilo images were obtained as described in Fig. 3. For this data, DOFx4 gave the best overall contrast and details. DOFx1, 8 and 12 are also shown here for comparison. Scale bar = 10 µm.

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Fig. 8
Fig. 8

Improvement to in vivo retinal image power spectrum following HiLo for rat #1. TOP CENTRE: Ratio plot of the normalized radial average energy of the FFT power spectrum of Uniform and HiLo images. All results are normalized by the Uniform image power spectrum, represented by a horizontal dash-dot line at ratio = 1.0. The horizontal axis represents spatial frequency in units of cycles/mm. INSET TOP LEFT: Magnified view at lower spatial frequencies. Low frequency information occupies a lower fraction of the energy spectrum after HiLo, due to removal of intra-ocular scatter. An example low frequency retinal feature - a blood vessel (~14 cycles/mm) is highlighted in the DOFx4 image at BOTTOM. INSET TOP RIGHT: Magnified view at medium spatial frequencies. Medium frequency information occupies a greater fraction of the energy spectrum after HiLo in DOFx4 compared to DOFx1. An example medium frequency feature - a nerve fibre bundle (86 cycles/mm) is highlighted at bottom.

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Fig. 9
Fig. 9

Example of in vivo AO retinal images obtained from another Long Evans rat (rat #2), showing two large blood vessels near a bifurcation. All images shown are the average of 82 frames and linearly stretched to fill the colormap for display purposes. Similar to Fig. 7, DOFx4 was considered most useful to enhance visualization of retinal features at this location. DOFx1, 8 and 12 are also shown here for comparison. Sensing wavelength = 670 nm, imaging wavelength = 532 nm. Scale bar = 10 µm.

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Equations (3)

Equations on this page are rendered with MathJax. Learn more.

I hp =HP( I u )
I lp =LP( C δ I u )
I hilo =η I lp + I hp

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