Oxygen-dependent diseases in the retina: Role of hypoxia-inducible factors

Experimental Eye Research

Volumn 83, Issue 3, 2006, Pages 473-483

  Arjamaa, Olli ^a   Nikinmaa, Mikko ^a  

^a Laboratory of Animal Physiology   (Finland)

Author keywords

diabetic retinopathy; erythropoietin; glaucoma; high altitude retinopathy; hypoxia inducible factor; oxygen; oxygen measurement; retina; retinal circulation; retinitis pigmentosa; retinopathy of prematurity; vascular endothelial growth factor; von Hippel Lindau disease

Indexed keywords

CHEMOTIN; CYCLOOXYGENASE 2 INHIBITOR; CYCLOSPORIN A; DNA TOPOISOMERASE INHIBITOR; ERYTHROPOIETIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 1BETA; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; OXYGEN; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; PROTEIN INHIBITOR; PROTEIN SUBUNIT; QUINOCARMYCIN; TOPOTECAN; UNCLASSIFIED DRUG; VASCULOTROPIN;

ALTITUDE DISEASE; ANGIOGENESIS; CELL TRANSPLANTATION; DIABETIC RETINOPATHY; DOWN REGULATION; ENZYME INHIBITION; GENE ACTIVATION; GENE REPLACEMENT THERAPY; GLAUCOMA; HIGH ALTITUDE RETINOPATHY; HUMAN; HYPOXEMIA; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; OXIDATION; OXYGEN TISSUE LEVEL; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FAMILY; RETINA BLOOD FLOW; RETINA CELL; RETINA DISEASE; RETINITIS PIGMENTOSA; RETROLENTAL FIBROPLASIA; REVIEW; TISSUE PERFUSION; VON HIPPEL LINDAU DISEASE;

CELL HYPOXIA; FEMALE; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; INFANT, NEWBORN; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; OXYGEN; RETINA; RETINAL DISEASES;

EID: 33745141162     PISSN: 00144835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exer.2006.01.016     Document Type: Review

References (123)

1. Aiello L.P., Avery R.L., et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal diseases. N. Engl. J. Med. 331 (1994) 1480-1487
2. Akiyama H., Tanaka T., et al. Visible light exposure induces VEGF gene expression through activation of retinoic acid receptor-alpha in retinoblastoma Y79 cells. Am. J. Physiol. 288 (2005) C913-C920
3. Baertschi A., Hausmaninger C., et al. Hypoxia-induced release of atrial natriuretic factor (ANF) from the isolated rat and rabbit heart. Biochem. Biophys. Res. Commun. 140 (1986) 427-433
4. Becerra S.P., and Amaral J. Erythropoietin-an endogenous retinal survival factor. N. Engl. J. Med. 347 (2002) 1968-1970
5. Berenbrink M., Koldkjaer P., et al. Evolution of oxygen secretion in fishes and the emergence of a complex physiological system. Science 307 (2005) 1752-1757
6. Berra E., Benizri E., et al. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J. 22 (2003) 4082-4090
7. Binley K., Askham Z., et al. Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy. Blood 100 (2002) 2406-2413
8. Bracken C.P., Whitelaw M.L., and Peet D.J. The hypoxia-inducible factors: key transcriptional regulators of hypoxic responses. Cell Mol. Life Sci. 60 (2003) 1376-1396
9. Brafman A., Mett I., et al. Inhibition of oxygen-induced retinopathy in RTP801-deficient mice. Invest. Ophthamol. Vis. Sci. 45 (2004) 3796-37805
10. Brahimi-Horn C., and Pouyssegur J. When hypoxia signalling meets the ubiquitin-proteasomal pathway, new targets for cancer therapy. Crit. Rev. Oncol. Hematol. 53 (2005) 115-123
11. Buchler P., Reber H.A., et al. Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer. Pancreas 26 (2003) 56-64
12. Cai Z., Manalo D.J., et al. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation 108 (2003) 79-85
13. Campochiaro P.A., and Hackett S.F. Ocular neovascularization: a valuable model system. Oncogene 22 (2003) 6537-6548
14. Carmeliet P., Dor Y., et al. Role of HIF-1 alpha in hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis. Nature 394 (1998) 485-490
15. Catrina S.B., Okamoto K., et al. Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes 53 (2004) 3226-3232
16. Chae H., Kim S.C., et al. Hypoxia induces apoptosis by caspase activation accompanying cytochrome C release from mitochondria in MC3T3E1 osteoblasts. p38 MAPK is related in hypoxia-induced apoptosis. Immunopharmacol. Immunotoxicol. 23 (2001) 133-152
17. Chavez J.C., Almhanna K., et al. Transient expression of hypoxia-inducible factor-1 alpha and target genes in peripheral nerves from diabetic rats. Neurosci. Lett. 374 (2005) 179-182
18. Cherniak N.S. Oxygen sensing: application in humans. J. Appl. Physiol. 96 (2004) 352-358
19. Czyzyk-Krzeska M.F., and Meller J. von Hippel-Lindau tumor suppressor: not only HIF's executioner. Trends Mol. Med. 10 (2004) 146-149
20. Delaey C., and Van de Voorde J. Regulatory mechanisms in the retinal and choroidal circulation. Ophthal. Res. 32 (2000) 249-256
21. Ebert B.L., and Bunn H.F. Regulation of erythropoietin gene. Blood 94 (1999) 1864-1877
22. Eichler W., Yafai Y., et al. PEDF derived from glial Muller cells: possible regulator of retinal angiogenesis. Exp. Cell Res. 299 (2004) 68-78
23. Eichler W., Yafai Y., et al. Angiogenesis-related factors derived from retinal glial (Muller) cells in hypoxia. Neuroreport 15 (2004) 1633-1637
24. Epstein A.C., Gleadle J.M., et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107 (2001) 43-45
25. Ferris F., Davis M.D., et al. Treatment of diabetic retinopathy. N. Engl. J. Med. 341 (1999) 667-678
26. 2 deprivation, reduced flow, and temperature on release of ANP from rabbit hearts. Am. J. Physiol. 268 (1995) H2352-H2357
27. Frayser R., Houston C.S., et al. Retinal hemorrhages at high altitude. N. Engl. J. Med. 282 (1970) 1183-1184
28. George D.J., and Kaelin W.G. The von Hippel-Lindau protein, endothelial growth factor, and kidney cancer. N. Engl. J. Med. 349 (2003) 419-421
29. Giacca A., Simon M., et al. The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes Dev. 18 (2004) 2183-2194
30. Gibson J., Cossins A., et al. Oxygen-sensitive membrane transporters in vertebrate red cells. J. Exp. Biol. 203 (2000) 1395-1407
31. Grimm C., Wentzel A., et al. HIF-1-induced erythtropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat. Med. 8 (2002) 718-724
32. Grimm C., Wentzel A., et al. Constitutive overexpression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration. J. Neurosci. 24 (2004) 5651-5658
33. Harris M.I., Flegal K.M., et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the Third National Health and Nutrition Examination Survey, 1998-1994. Diabetes Care 28 (1998) 518-524
34. Henkind P., Hansen R.I., et al. Ocular circulation. In: Records R.E. (Ed). Physiology of the Human Eye and Visual System (1979), Harper and Row, New York 98-155
35. Hewitson K.S., and Schofield C.J. The HIF pathway as a therapeutic target. Drug Discov. Today 9 (2004) 704-711
36. Hewitson K.S., McNeill L.A., et al. Hypoxia-inducible factor (HIF) asparagines hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J. Biol. Chem. 277 (2002) 26351-26355
37. Huang L.E., Arany Z., et al. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J. Biol. Chem. 271 (1996) 32253-32259
38. 2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 7987-7992
39. Iida K., Okimura Y., et al. A variety of phenotype with R161Q germline mutation of the von Hippel-Lindau tumor suppressor gene in Japanese kindred. Int. J. Mol. Med. 13 (2004) 401-404
40. Isaacs J.S., Jung Y.J., et al. Aryl hydrocarbon nuclear translocator (ARNT) promotes oxygen-independent stabilization of hypoxia-inducible factor-1alpha by modulating an Hsp90-dependent regulatory pathway. J. Biol. Chem. 279 (2004) 16128-16135
41. Itakura H., Kishi S., et al. Persistent secretion of vascular endothelial growth factor into the vitreous cavity in proliferative diabetic retinopathy after vitrectomy. Ophthalmology 111 (2004) 1880-1884
42. Iyer N.V., and Leung S.W. The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation. Genomics 52 (1998) 159-165
43. 2-regulated prolyl hydroxylation. Science 292 (2001) 468-472
44. Jelkmann W. Molecular biology of erythropoietin. Intern. Med. 43 (2004) 649-659
45. Jeong J.O., Byun J., et al. Improved expression by cytomegalovirus promoter/enhancer and behaviour of vascular endothelial growth gene factor after myocardial injection of naked DNA. Exp. Mol. Biol. 34 (2002) 278-284
46. Jewell U.R., Kvietikova I., et al. Induction of HIF-1alpha in response to hypoxia is instantaneous. FASEB J. 15 (2001) 1312-1314
47. Kaelin W.G. Proline hydroxylation and gene expression. Annu. Rev. Biochem. 74 (2005) 115-128
48. Kallio P.J., Pongratz I., et al. Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor. Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 5667-5672
49. Katschinski D.M., Le L., et al. Interaction of the PAS B domain with HSP90 accelerates hypoxia-inducible factor-1alpha stabilization. Cell Physiol. Biochem. 14 (2004) 351-360
50. Kim W.Y., and Kaelin W.G. Role of VHL gene mutation in human cancer. J. Clin. Oncol. 22 (2004) 4991-5004
51. Klinger J., Pietras L., et al. Reduced oxygen tension increases atrial natriuretic peptide release from atrial cardiocytes. Exp. Biol. Med. 226 (2001) 847-855
52. Knowles H.J., Raval R.R., et al. Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res. 63 (2003) 1764-1768
53. Kung A.L., Zabludoff S.D., et al. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 6 (2004) 33-43
54. Lang G.E., and Kuba G.B. High-altitude retinopathy. Am. J. Ophthalmol. 123 (1997) 418-420
55. Lee S.H., Wolf P.L., et al. Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N. Engl. J. Med. 342 (2000) 626-633
56. Lee M., Rentz J., et al. Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer. Gene Ther. 10 (2003) 1535-1542
57. Lee J.-W., Bae S.-H., et al. Hypoxia-inducible factor (HIF-1) alpha: Its protein stability and biological actions. Exp. Mol. Med. 36 (2004) 1-12
58. Lew R., and Baertschi A. Mechanisms of hypoxia-induced atrial natriuretic factor release from rat hearts. Am. J. Physiol. 257 (1989) H147-H156
59. Li H., Ko H.P., et al. Induction of phosphoglycerate kinase 1 gene expression by hypoxia. Roles of ARNT and HIF1alpha. J. Biol. Chem. 271 (1996) 21262-21267
60. Ljusegren M., and Andersson R. Hypoxia induces release of atrial natriuretic peptide in rat atrial tissue: a role for this peptide during low oxygen stress. Naunyn Schmiedebergs Arch. Pharmacol. 350 (1994) 189-193
61. Lutty G.A., and McLeod D.S. Retinal vascular development and oxygen-induced retinopathy: a role for adenosine. Prog. Retin. Eye Res. 22 (2003) 95-111
62. Lopez-Barneo J., Pardal R., and Ortega-Saenz P. Cellular mechanisms of oxygen sensing. Annu. Rev. Physiol. 63 (2001) 259-287
63. Ma W., Tessarollo L., et al. Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene. Cancer Res. 63 (2003) 5320-5328
64. Mahon P.C., Hirota K., et al. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 15 (2001) 2675-2686
65. Makino Y., Cao R., et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 14 (2001) 550-554
66. Marti H.H. Erythropoietin and the hypoxic brain. J. Exp. Biol. 207 (2004) 3233-3242
67. Marti H.H., Bernaudin M., et al. Neuroprotection and angiogenesis: Dual role of erythropoietin in brain ischemia. News Physiol. Sci. 15 (2000) 225-229
68. McColm J.R., Geisen P., et al. VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP. Mol. Vis. 10 (2004) 512-520
69. Minet E., Mottet D., et al. Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction. FEBS Lett. 460 (1999) 251-256
70. Mino R.P., Spoerri P.E., et al. Adenosine receptor antagonists and retinal neovascularization in vivo. Invest. Ophthalmol. Vis. Sci. 42 (2001) 3320-3324
71. Morita M., Ohneda O., et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity: association with erythropoietin. EMBO J. 22 (2003) 1134-1146
72. Mullner-Eidenbock A., Rainer G., et al. High-altitude retinopathy and retinal vascular dysregulation. Eye 5 (2000) 724-729
73. Naskar R., and Dreyer E.B. New horizons in neuroprotection. Surv. Ophthalmol. 45 Supp. 3 (2001) S250-S255
74. Neckers L., and Ivy S.P. Heat shock protein 90. Curr. Opin. Oncol. 15 (2003) 419-424
75. Nikinmaa M., and Rees B.B. Oxygen-dependent gene expression in fishes. Am. J. Physiol. 288 (2005) R1079-R1090
76. Ogunyemi D., Koos B., et al. Adenosine modulates hypoxia-induced atrial natriuretic peptide release in fetal sheep. Am. J. Physiol. 269 (1995) H282-H287
77. Ozaki H., Yu A.Y., et al. Hypoxia-inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest. Ophthalmol. Vis. Sci. 40 (1999) 82-189
78. Pagés G., and Pouysségur J. Transcriptional regulation of the vascular endothelial growth factor gene-a concert of activating factors. Cardiovasc. Res. 65 (2005) 564-573
79. Pajusola K., Kunnapuu J., et al. Stabilized HIF-1alpha is superior to VEGF for angiogenesis in skeletal muscle via adeno-associated virus gene transfer. FASEB J. 19 (2005) 1365-1367
80. Paul S.A.M., Simons J.W., et al. HIF at the crossroads between ischemia and carcinogenesis. J. Cell. Physiol. 200 (2004) 20-30
81. Penn J.S., Li S., and Naash M.I. Ambient hypoxia reverses retinal vascular attenuation in a transgenic mouse model of autosomal dominant retinitis pigmentosa. Invest. Ophthalmol. 41 (2000) 4007-4013
82. Pierce E.A., Avery R.L., et al. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 905-909
83. Pillunat L.E. Ocular blood flow endpoints. Eur. J. Ophthalmol. 9 Suppl. 1 (1999) S44-S47
84. Poulaki V., Qin W., et al. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. J. Clin. Invest. 109 (2002) 805-815
85. Pugh C.W., and Ratcliffe P.J. Regulation of angiogenesis by hypoxia: Role of the HIF system. Nat. Med. 9 (2003) 677-684
86. Resnikoff S., Pascolini D., et al. Global data on visual impairment in the year 2002. Bull. WHO. 82 (2002) 844-851
87. Ribatti D. The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a historical review. Br. J. Haematol. 128 (2005) 303-309
88. Rolling F. Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives. Gene Ther. 1 Suppl. (2005) S26-S32
89. Semenza G. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J. Appl. Physiol. 88 (2000) 1474-1480
90. Semenza G.L. Hydroxylation of HIF-1: Oxygen sensing at the molecular level. Physiology 19 (2004) 176-182
91. Semenza G.L., and Wang G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell Biol. 12 (1992) 5447-5454
92. Schoch H.J., Fischer S., et al. Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain. Brain 125 (2002) 2549-2557
93. Shams I., Avivi A., et al. Hypoxic stress tolerance of the blind subterranean mole rat: Expression of eythropoietin and hypoxia-inducible factor 1 alpha. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 9698-9703
94. Shams I., Nevo E., et al. Ontogenic expression of erythropoietin and hypoxia-inducible factor-1 alpha genes in subterranean blind mole rats. FASEB J. 19 (2005) 307-309
95. Shortt A.J., Howell K., et al. Chronic systemic hypoxia causes intra-retinal angiogenesis. J. Anat. 205 (2004) 349-356
96. Shuin T., Yamazaki I., et al. Recent advances in ideas on the molecular pathology and clinical aspects of von Hippel-Lindau disease. Int. J. Clin. Oncol. 9 (2004) 283-287
97. Skvorak J., Sutton E., et al. Mechanisms of anoxia-induced atrial natriuretic peptide release in the isolated rat atria. Am. J. Physiol. 271 (1996) R237-R243
98. Smith L.E. Pathogenesis of retinopathy of prematurity. Semin. Neonatol. 8 (2003) 469-473
99. Stecyk J., Stenslökken K.-O., et al. Maintained cardiac pumping in anoxic Crucian carp. Science 306 (2004) 77
100. Stefánsson E. The therapeutic effects of retinal laser treatment and vitrectomy. A theory based on oxygen and vascular physiology. Acta Ophthalmol. Scand 79 (2001) 435-445
101. Synnestvedt K., Furuta G.T., et al. Ecto-5'-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J. Clin. Invest. 110 (2002) 993-1002
102. Tan C., de Noronha R.G., et al. Identification of a novel small-molecule inhibitor of the hypoxia-inducible factor 1 pathway. Cancer Res. 65 (2005) 605-612
103. Tezel G., and Wax M.B. Hypoxia-inducible factor 1alpha in the glaucomatous retina and optic nerve head. Arch. Ophthalmol. 122 (2004) 1348-1356
104. Toth M., Vuorinen K., et al. Hypoxia stimulates the release of ANP and BNP from perfused rat ventricular myocardium. Am. J. Physiol. 266 (1994) H1572-H1580
105. Trick G.L., and Berkowitz B.A. Retinal oxygenation response and retinopathy. Prog. Ret. Eye Res. 24 (2005) 259-274
106. Vannay A., Dunai G., et al. Association of genetic polymorphisms of vascular endothelial growth factor and risk for proliferative retinopathy of prematurity. Pediatr. Res. 57 (2005) 396-398
107. Vengellur A., Woods B.G., et al. Gene expression profiling of the hypoxia-signalling pathway in hypoxia-inducible factor 1alpha null mouse embryonic fibroblasts. Gene Expression 11 (2003) 181-197
108. 2 tension. Proc. Natl. Acad. Sci. 92 (1995) 5510-5514 USA
109. Wangsa-Wirawan N.D., and Linsenmeier R.A. Retinal oxygen. Fundamental and clinical aspects. Arch. Ophthalmol. 121 (2003) 547-557
110. Watanabe D., Suzuma K., et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N. Engl. J. Med. 353 (2005) 782-792
111. Weiss M.J. New insights into erythropoietin and epoetin alfa: mechanisms of action, target tissues, and clinical application. Oncologist 8 Suppl 3 (2003) 18-29
112. Wenger R.H., Kvietikova I., et al. Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level. Kidney Int. 51 (1997) 560-563
113. Werdich X.Q., McCollum G.W., et al. Variable oxygen and retinal VEGF levels: correlation with incidence and severity of pathology in a rat model of oxygen-induced retinopathy. Exp. Eye Res. 79 (2004) 623-630
114. Wiedman M., and Tabin G.C. High-altitude retinopathy and altitude illness. Ophthalmology 106 (1999) 1924-1926
115. Wiesener M.S., Turley H., et al. Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92 (1998) 260-2268
116. Wilkinson-Berka J.L. Vasoactive factors and diabetic retinopathy: vascular endothelial growth factor, cyclooxygenase-2 and nitric oxide. Curr. Pharm. Des. 10 (2004) 3331-3341
117. Witmer A.N., Vrensen G.F., et al. Vascular endothelial growth factors and angiogenesis in eye disease. Prog. Retin. Eye Res. 22 (2003) 1-29
118. Xu T., Jiao J., et al. ATP-sensitive potassium channels regulate stimulated ANF secretion in isolated rat heart. Am. J. Physiol. 271 (1996) H2339-H2345
119. 2+/calmodulin kinase-dependent activation of hypoxia-inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxia. J. Biol. Chem. 280 (2005) 4321-4328
120. Zhang H.R. Scanning electron-microscopic study of corrosion casts on retinal and choroidal angioarchitecture in man and animals. Prog. Ret. Eye Res. 13 (1994) 243-270
121. Zhang S.X., Ma J.X., et al. Genetic difference in susceptibility to the blood-retina barrier breakdown in diabetes and oxygen-induced retinopathy. Am. J. Pathol. 166 (2005) 313-321
122. Zhu H., and Bunn H.F. How do cells sense oxygen?. Science 292 (2001) 449-451
123. Zimmet P., Alberti K.G.M.M., et al. Global and societal implications of the diabetes epidemic. Nature 414 (2001) 782-787