Abstract

Maps of the oxygen distribution in the retina of the mouse eye were obtained by phosphorescence-lifetime imaging. Phosphor dissolved in the blood was excited by modulated light and phosphorescence imaged through microscope optics with an intensified-CCD camera. Phosphorescence lifetimes and oxygen pressures were calculated for each pixel of the images. The resolution was sufficient to permit the detection of anomalies that result in reduced oxygen pressures in individual retinal capillaries. High-resolution maps of oxygen distribution in the retina can provide greater understanding of the role of oxygen and vascular function in diseases of the eye.

© 2005 Optical Society of America

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  9. E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).
  10. J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).
  11. D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
    [PubMed]
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    [CrossRef] [PubMed]
  13. R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).
  14. R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
    [CrossRef]
  15. S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).
  16. S. Blumenröder, A. J. Augustin, F. H. J. Koch, “The influence of intraocular pressure and systemic oxygen tension on the intravascular p O2 of the pig retina as measured with phosphorescence quenching,” Surv. Ophthalmol. 42, S118–S126 (1997).
    [CrossRef]
  17. R. D. Shonat, A. C. Kight, “Frequency domain imaging of oxygen tension in the mouse retina,” Adv. Exp. Med. Biol. 510, 243–247 (2003).
    [CrossRef]
  18. R. D. Shonat, A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31, 1084–1096 (2003b).
    [CrossRef] [PubMed]
  19. S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
    [CrossRef] [PubMed]
  20. S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
    [CrossRef]
  21. I. Dunphy, S. A. Vinogradov, D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence,” Anal. Biochem. 310, 191–198 (2002).
    [CrossRef] [PubMed]
  22. V. Rozhkov, D. F. Wilson, S. Vinogradov, “Tuning oxygen quenching constants using dendritic encapsulation of phosphorescent Pd-porphyrins,” Polym. Mater. Sci. Eng. 85, 601–603 (2001).
  23. S. A. Vinogradov, D. F. Wilson, “Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements,” J. Chem. Soc. Perkin Trans. 2, 103–111 (1995).
    [CrossRef]
  24. S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
    [CrossRef]
  25. D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
    [CrossRef]
  26. M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
    [CrossRef]
  27. D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
    [PubMed]
  28. D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).
  29. D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
    [PubMed]

2005 (1)

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

2003 (2)

R. D. Shonat, A. C. Kight, “Frequency domain imaging of oxygen tension in the mouse retina,” Adv. Exp. Med. Biol. 510, 243–247 (2003).
[CrossRef]

R. D. Shonat, A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31, 1084–1096 (2003b).
[CrossRef] [PubMed]

2002 (1)

I. Dunphy, S. A. Vinogradov, D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence,” Anal. Biochem. 310, 191–198 (2002).
[CrossRef] [PubMed]

2001 (2)

V. Rozhkov, D. F. Wilson, S. Vinogradov, “Tuning oxygen quenching constants using dendritic encapsulation of phosphorescent Pd-porphyrins,” Polym. Mater. Sci. Eng. 85, 601–603 (2001).

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
[CrossRef]

2000 (1)

D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
[PubMed]

1999 (3)

D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

1998 (3)

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
[CrossRef]

1997 (2)

A. M. Maguire, “Management of diabetic retinopathy,” J. Am. Osteopathic Assoc. 97, S6–S11 (1997).

S. Blumenröder, A. J. Augustin, F. H. J. Koch, “The influence of intraocular pressure and systemic oxygen tension on the intravascular p O2 of the pig retina as measured with phosphorescence quenching,” Surv. Ophthalmol. 42, S118–S126 (1997).
[CrossRef]

1996 (4)

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

1995 (2)

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

S. A. Vinogradov, D. F. Wilson, “Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements,” J. Chem. Soc. Perkin Trans. 2, 103–111 (1995).
[CrossRef]

1994 (2)

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

1992 (2)

R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).

R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
[CrossRef]

1988 (2)

D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
[PubMed]

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring the distribution of oxygen in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

1986 (1)

R. A. Linsenmeier, “Effects of light and darkness on oxygen distribution and consumption in the cat retina.” J. Gen. Physiol. 88, 521–542 (1986).

Adamis, A. P.

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Ahmed, J.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

Aiello, I. P.

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

Alder, V.

D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).

Alder, V. A.

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

Aouidid, S.

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

Augustin, A. J.

S. Blumenröder, A. J. Augustin, F. H. J. Koch, “The influence of intraocular pressure and systemic oxygen tension on the intravascular p O2 of the pig retina as measured with phosphorescence quenching,” Surv. Ophthalmol. 42, S118–S126 (1997).
[CrossRef]

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

Avery, R. L.

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

Berkowitz, B. A.

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

Bernal, M. T.

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

Berse, B.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Blumenröder, S.

S. Blumenröder, A. J. Augustin, F. H. J. Koch, “The influence of intraocular pressure and systemic oxygen tension on the intravascular p O2 of the pig retina as measured with phosphorescence quenching,” Surv. Ophthalmol. 42, S118–S126 (1997).
[CrossRef]

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

Braun, R. D.

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

Brown, L. F.

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Buerk, D. G.

D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
[CrossRef]

Burns, M.

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

Chan-Ling, T.

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

Cranstoun, S. D.

R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).

Cringle, S.

D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
[PubMed]

Cringle, S. J.

D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

D’Amico, D. I.

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

D’Amore, P. A.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Dewhirst, M. W.

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

Dorey, C. K.

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

Dugan, B. W.

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
[CrossRef]

Dunphy, I.

I. Dunphy, S. A. Vinogradov, D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence,” Anal. Biochem. 310, 191–198 (2002).
[CrossRef] [PubMed]

Dvorak, H. F.

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Evans, S. M.

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

Fernandez-Seara, M. A.

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
[CrossRef]

Foley, E. D.

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

Folkman, J.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

Frank, R. N.

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

Gnessin, H.

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

Green, T. I.

D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
[PubMed]

Grus, F.

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

Hatchell, D. L.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

Hohman, T. C.

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

Intaglietta, M.

D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
[CrossRef]

Itin, A.

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

James, W. A.

F. A. L’Esperance, W. A. James, “The eye and Diabetes mellitus,” in Diabetes Mellitus: Theory and Practice, M. Ellenberg, H. Rifkin, eds., 3rd ed. (Medical Examination, pp. 727–7571983).

Jenkins, W. T.

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

Johnson, P. C.

D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
[CrossRef]

Kern, T. S.

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

Keshet, E.

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

Kight, A. C.

R. D. Shonat, A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31, 1084–1096 (2003b).
[CrossRef] [PubMed]

R. D. Shonat, A. C. Kight, “Frequency domain imaging of oxygen tension in the mouse retina,” Adv. Exp. Med. Biol. 510, 243–247 (2003).
[CrossRef]

Klitzman, B.

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

Koch, C.

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

Koch, F.

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

Koch, F. H. J.

S. Blumenröder, A. J. Augustin, F. H. J. Koch, “The influence of intraocular pressure and systemic oxygen tension on the intravascular p O2 of the pig retina as measured with phosphorescence quenching,” Surv. Ophthalmol. 42, S118–S126 (1997).
[CrossRef]

Kowluru, R. A.

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

Ku, P.

D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
[PubMed]

L’Esperance, F. A.

F. A. L’Esperance, W. A. James, “The eye and Diabetes mellitus,” in Diabetes Mellitus: Theory and Practice, M. Ellenberg, H. Rifkin, eds., 3rd ed. (Medical Examination, pp. 727–7571983).

Lee, W. M. F.

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

Linsenmeier, R. A.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

R. A. Linsenmeier, “Effects of light and darkness on oxygen distribution and consumption in the cat retina.” J. Gen. Physiol. 88, 521–542 (1986).

Lo, L.-W.

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

Lutty, G. A.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

Maguire, A. M.

A. M. Maguire, “Management of diabetic retinopathy,” J. Am. Osteopathic Assoc. 97, S6–S11 (1997).

McLeod, D. S.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

McRipley, M. A.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

Miller, J. W.

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Moulton, R. S.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

O’Reilly, M. S.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Ong, E. T.

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

Padnick, L. B.

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

Pawlowski, M.

R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
[CrossRef]

Pe’re, J.

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

Pierce, E. A.

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

Prakash, M.

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

Reynaud, X.

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

Riva, C. E.

R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
[CrossRef]

Riva, G. E.

R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).

Rozhkov, V.

V. Rozhkov, D. F. Wilson, S. Vinogradov, “Tuning oxygen quenching constants using dendritic encapsulation of phosphorescent Pd-porphyrins,” Polym. Mater. Sci. Eng. 85, 601–603 (2001).

Rumsey, W. L.

D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
[PubMed]

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring the distribution of oxygen in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

Sehgal, C.

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

Shima, D. T.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Shonat, R. D.

R. D. Shonat, A. C. Kight, “Frequency domain imaging of oxygen tension in the mouse retina,” Adv. Exp. Med. Biol. 510, 243–247 (2003).
[CrossRef]

R. D. Shonat, A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31, 1084–1096 (2003b).
[CrossRef] [PubMed]

R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).

R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
[CrossRef]

Smith, B.

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

Smith, L. E. H.

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

Spitznas, M.

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

Stone, J.

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

Su, E. N.

D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

Su, E.-N.

D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
[PubMed]

Tsai, A. G.

D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
[CrossRef]

Vanderkooi, J. M.

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring the distribution of oxygen in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
[PubMed]

Vinogradov, S.

V. Rozhkov, D. F. Wilson, S. Vinogradov, “Tuning oxygen quenching constants using dendritic encapsulation of phosphorescent Pd-porphyrins,” Polym. Mater. Sci. Eng. 85, 601–603 (2001).

Vinogradov, S. A.

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

I. Dunphy, S. A. Vinogradov, D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence,” Anal. Biochem. 310, 191–198 (2002).
[CrossRef] [PubMed]

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
[CrossRef]

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

S. A. Vinogradov, D. F. Wilson, “Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements,” J. Chem. Soc. Perkin Trans. 2, 103–111 (1995).
[CrossRef]

Wilson, D. E.

R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
[CrossRef]

R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).

Wilson, D. F.

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

I. Dunphy, S. A. Vinogradov, D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence,” Anal. Biochem. 310, 191–198 (2002).
[CrossRef] [PubMed]

V. Rozhkov, D. F. Wilson, S. Vinogradov, “Tuning oxygen quenching constants using dendritic encapsulation of phosphorescent Pd-porphyrins,” Polym. Mater. Sci. Eng. 85, 601–603 (2001).

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
[CrossRef]

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

S. A. Vinogradov, D. F. Wilson, “Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements,” J. Chem. Soc. Perkin Trans. 2, 103–111 (1995).
[CrossRef]

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring the distribution of oxygen in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
[PubMed]

Yeo, K.-T.

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

Yeo, T.-K.

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Yu, D. Y.

D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
[PubMed]

D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

Ziemer, S. L.

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

Adv. Exp. Biol. Med. (1)

D. G. Buerk, A. G. Tsai, M. Intaglietta, P. C. Johnson, “Comparing tissue PO2 measurements by recessed microelectrode and phosphorescence quenching,” Adv. Exp. Biol. Med. 454, 367–374 (1998).
[CrossRef]

Adv. Exp. Med. Biol. (2)

R. D. Shonat, A. C. Kight, “Frequency domain imaging of oxygen tension in the mouse retina,” Adv. Exp. Med. Biol. 510, 243–247 (2003).
[CrossRef]

S. Blumenröder, A. J. Augustin, M. Spitznas, F. Koch, F. Grus, “Retino-choroidal oxygen imaging through a fundus camera,” Adv. Exp. Med. Biol. 388, 35–39 (1996).
[CrossRef] [PubMed]

Am. J. Ophthalmol. (1)

A. P. Adamis, J. W. Miller, M. T. Bernal, D. I. D’Amico, J. Folkman, T.-K. Yeo, K.-T. Yeo, “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” Am. J. Ophthalmol. 118, 445–450 (1994).
[PubMed]

Am. J. Pathol. (1)

J. W. Miller, A. P. Adamis, D. T. Shima, P. A. D’Amore, R. S. Moulton, M. S. O’Reilly, J. Folkman, H. F. Dvorak, L. F. Brown, B. Berse, T.-K. Yeo, K.-T. Yeo, “Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model,” Am. J. Pathol. 145, 574–584 (1994).

Am. J. Physiol. (1)

D. Y. Yu, V. A. Alder, S. J. Cringle, E. N. Su, M. Burns, “Intraretinal oxygen distribution in urethane-induced retinopathy in rats,” Am. J. Physiol. 274, H2009–H2017 (1998).
[PubMed]

Anal. Biochem. (1)

I. Dunphy, S. A. Vinogradov, D. F. Wilson, “Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence,” Anal. Biochem. 310, 191–198 (2002).
[CrossRef] [PubMed]

Ann. Biomed. Eng. (1)

R. D. Shonat, A. C. Kight, “Oxygen tension imaging in the mouse retina,” Ann. Biomed. Eng. 31, 1084–1096 (2003b).
[CrossRef] [PubMed]

Appl. Opt. (1)

R. D. Shonat, D. E. Wilson, C. E. Riva, M. Pawlowski, “Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method,” Appl. Opt. 33, 3711–3718 (1992).
[CrossRef]

Arch. Ophthalmol. (1)

C. K. Dorey, S. Aouidid, X. Reynaud, H. F. Dvorak, L. F. Brown, “Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat,” Arch. Ophthalmol. 114, 1210–1217 (1996); erratum Arch. Ophthalmol.115, 192 (1997).
[CrossRef] [PubMed]

Biophys. J. (1)

S. A. Vinogradov, L.-W. Lo, W. T. Jenkins, S. M. Evans, C. Koch, D. F. Wilson, “Noninvasive imaging of the distribution of oxygen in tissue in vivo using near infra-red phosphors,” Biophys. J. 70, 1609–1617 (1996).

Brit. J. Cancer (1)

M. W. Dewhirst, E. T. Ong, R. D. Braun, B. Smith, B. Klitzman, S. M. Evans, D. F. Wilson, “Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia,” Brit. J. Cancer 79, 1717–1722 (1999).
[CrossRef]

Invest Ophthalmol. Visual Sci. (1)

J. Stone, T. Chan-Ling, J. Pe’re, A. Itin, H. Gnessin, E. Keshet, “Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity,” Invest Ophthalmol. Visual Sci. 37, 290–299 (1996).

Invest. Ophthalmol. Vis. Sci. (1)

D. Y. Yu, S. Cringle, E.-N. Su, P. Ku, “Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat,” Invest. Ophthalmol. Vis. Sci. 41, 3999–4006 (2000).
[PubMed]

Invest. Ophthalmol. Visual Sci. (4)

D. Y. Yu, S. J. Cringle, V. Alder, E. N. Su, “Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia,” Invest. Ophthalmol. Visual Sci. 40, 2082–2087 (1999).

R. D. Shonat, D. E. Wilson, G. E. Riva, S. D. Cranstoun, “Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats,” Invest. Ophthalmol. Visual Sci. 33, 3174–3180 (1992).

R. A. Linsenmeier, R. D. Braun, M. A. McRipley, L. B. Padnick, J. Ahmed, D. L. Hatchell, D. S. McLeod, G. A. Lutty, “Retinal hypoxia in long-term diabetic cats,” Invest. Ophthalmol. Visual Sci. 39, 1647–1657 (1998).

B. A. Berkowitz, R. A. Kowluru, R. N. Frank, T. S. Kern, T. C. Hohman, M. Prakash, “Subnormal retinal oxygenation response precedes diabetic-like retinopathy,” Invest. Ophthalmol. Visual Sci. 40, 2100–2105 (1999).

J. Am. Osteopathic Assoc. (1)

A. M. Maguire, “Management of diabetic retinopathy,” J. Am. Osteopathic Assoc. 97, S6–S11 (1997).

J. Appl. Physiol. (1)

S. L. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, D. F. Wilson, “Oxygen distribution in murine tumors: characterization using oxygen dependent quenching of phosphorescence,” J. Appl. Physiol. 98, 1503–1510 (2005).
[CrossRef]

J. Biol. Chem. (1)

D. F. Wilson, W. L. Rumsey, T. I. Green, J. M. Vanderkooi, “The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen,” J. Biol. Chem. 263, 2712–2718 (1988).
[PubMed]

J. Chem. Soc. Perkin Trans. (1)

S. A. Vinogradov, D. F. Wilson, “Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements,” J. Chem. Soc. Perkin Trans. 2, 103–111 (1995).
[CrossRef]

J. Gen. Physiol. (1)

R. A. Linsenmeier, “Effects of light and darkness on oxygen distribution and consumption in the cat retina.” J. Gen. Physiol. 88, 521–542 (1986).

Polym. Mater. Sci. Eng. (1)

V. Rozhkov, D. F. Wilson, S. Vinogradov, “Tuning oxygen quenching constants using dendritic encapsulation of phosphorescent Pd-porphyrins,” Polym. Mater. Sci. Eng. 85, 601–603 (2001).

Proc. Natl. Acad. Sci. USA (1)

E. A. Pierce, R. L. Avery, E. D. Foley, I. P. Aiello, L. E. H. Smith, “Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization,” Proc. Natl. Acad. Sci. USA 92, 905–909 (1995).

Rev. Sci. Instrum. (1)

S. A. Vinogradov, M. A. Fernandez-Seara, B. W. Dugan, D. F. Wilson, “Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples,” Rev. Sci. Instrum. 72, 3396–3406 (2001).
[CrossRef]

Science (1)

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring the distribution of oxygen in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

Surv. Ophthalmol. (1)

S. Blumenröder, A. J. Augustin, F. H. J. Koch, “The influence of intraocular pressure and systemic oxygen tension on the intravascular p O2 of the pig retina as measured with phosphorescence quenching,” Surv. Ophthalmol. 42, S118–S126 (1997).
[CrossRef]

Other (1)

F. A. L’Esperance, W. A. James, “The eye and Diabetes mellitus,” in Diabetes Mellitus: Theory and Practice, M. Ellenberg, H. Rifkin, eds., 3rd ed. (Medical Examination, pp. 727–7571983).

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Figures (7)

Fig. 1
Fig. 1

Images of the phosphorescence intensity from the retina of the mouse eye. The mouse was treated as described in Section 2, and the phosphorescence intensity images were collected at 1030 Hz. The number on each image indicates the delay (in degrees) relative to the excitation for which the image was collected. The retinal area imaged is approximately 0.92 mm high by 1.2 mm wide.

Fig. 2
Fig. 2

Phosphorescence intensity versus phase delay (in degrees) for three regions of interest in the image, two veins and one arteriole. Least-squares fits to a sinusoid yielded phase shifts of 43.6° and 40.4° for the veins and 35.1° for the arteriole. (Graphed in Origin.)

Fig. 3
Fig. 3

Maps of (a) the phosphorescence intensity at 30° phase shift, (b) the phase shift between excitation and phosphorescence, (c) the phosphorescence lifetime, and (d) the oxygen pressure calculated from the set of images in Fig. 1. The maps correspond to a region whose physical dimensions are 0.92 mm high by 1.2 mm wide. The oxygen maps were smoothed with a running-median 5 × 5 filter.

Fig. 4
Fig. 4

Dependence of the retinal oxygen pressures on time after induction of anesthesia. The mouse was given an intraperitoneal injection of anesthetic, the pupil was dilated, and retinal imaging of the phosphorescence lifetimes began ~3 min later. The measurements shown were made at 5 and 35 min after induction of anesthesia. The area of the retina that was imaged was approximately 0.92 mm high by 1.2 mm wide.

Fig. 5
Fig. 5

Time course of the oxygen pressures in the retinal veins and arterioles following anesthesia. Oxygen pressure maps of the retina were repetitively measured; a total of 19 measurements was made over the period of 3–35 minutes following anesthesia. Regions of interest were selected within two arterioles and two veins, and the average oxygen pressures for each region were determined at every time. The resultant values are plotted as a function of time after anesthesia.

Fig. 6
Fig. 6

Oxygen pressure maps of (a) the region containing two laser photocoagulation spots and (b) a region centered on one of the two spots. The measurements were made with modulation frequencies of 3030 and 800 Hz, respectively. The area of retina covered by the oxygen maps is approximately 0.92 mm high by 1.2 mm wide.

Fig. 7
Fig. 7

Phosphorescence intensity image (left) and oxygen pressure map (right) of the eye of a 2-year-old mouse. The measurements were made at 1000 Hz. The retinal area imaged was approximately 0.92 mm high by 1.2 mm wide.

Equations (8)

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Ex ( t ) = A sin ( 2 π f t ) + B ,
Em ( t ) = a sin ( 2 π f t - ϕ ) + b ,             ϕ = 2 π f × δ t ,
tan ( ϕ ) = 2 π f τ .
P ( t ) = A n = 1 sin ( 2 π n f t ) + B .
P ( t ) = n = 1 a n sin ( 2 π n f t - ϕ n ) + b ,             ϕ = 2 π n f × δ t n .
I ( Δ T ) = C Δ T 1 / f ( n = 1 a n sin ( 2 π n f t - ϕ n ) d t ) ,
I ( Δ T ) c × cos ( 2 π f Δ T - ϕ ) + d ,
τ 0 / τ = 1 + k Q × τ 0 × p O 2 ,

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