Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 Jul;151(1):13–23.

Vascular endothelial growth factor and ocular neovascularization.

J W Miller 1
PMCID: PMC1857918  PMID: 9212726

Abstract

Okamoto et al have developed an extremely useful and interesting model of retinal and subretinal neovascularization. Using molecular techniques, they have developed a transgenic model driven by overexpression of VEGF, a growth factor demonstrated to play an important role in neovascularization in many ocular diseases. They have been able to demonstrate that VEGF overexpression is sufficient to cause intraretinal and subretinal neovascularization. The mouse model is relatively cheap and reliable, does not require any exogenous agent, and has many characteristics of clinical intraocular neovascularization. The new vessels develop in the outer retina and subretinal space and have a characteristic histological appearance. They leak fluorescein on angiography, demonstrating their similarity to human disease and allowing identification and grading of neovascularization in vivo. The model can be used to investigate molecular mechanisms of VEGF-dependent neovascularization, with applications beyond ocular eye disease. The model can also be used to study anti-angiogenic agents that have the potential to treat common blinding diseases such as age-related macular degeneration. Okamoto et al have made a substantial contribution to the angiogenesis field with this work, and one looks forward to future investigations.

Full text

PDF
14

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ASHTON N. Retinal vascularization in health and disease: Proctor Award Lecture of the Association for Research in Ophthalmology. Am J Ophthalmol. 1957 Oct;44(4 Pt 2):7–17. doi: 10.1016/0002-9394(57)90426-9. [DOI] [PubMed] [Google Scholar]
  2. Adamis A. P., Miller J. W., Bernal M. T., D'Amico D. J., Folkman J., Yeo T. K., Yeo K. T. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol. 1994 Oct 15;118(4):445–450. doi: 10.1016/s0002-9394(14)75794-0. [DOI] [PubMed] [Google Scholar]
  3. Adamis A. P., Shima D. T., Tolentino M. J., Gragoudas E. S., Ferrara N., Folkman J., D'Amore P. A., Miller J. W. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol. 1996 Jan;114(1):66–71. doi: 10.1001/archopht.1996.01100130062010. [DOI] [PubMed] [Google Scholar]
  4. Aiello L. P., Avery R. L., Arrigg P. G., Keyt B. A., Jampel H. D., Shah S. T., Pasquale L. R., Thieme H., Iwamoto M. A., Park J. E. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480–1487. doi: 10.1056/NEJM199412013312203. [DOI] [PubMed] [Google Scholar]
  5. Aiello L. P., Pierce E. A., Foley E. D., Takagi H., Chen H., Riddle L., Ferrara N., King G. L., Smith L. E. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10457–10461. doi: 10.1073/pnas.92.23.10457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Amin R. H., Frank R. N., Kennedy A., Eliott D., Puklin J. E., Abrams G. W. Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 1997 Jan;38(1):36–47. [PubMed] [Google Scholar]
  7. Antonelli-Orlidge A., Saunders K. B., Smith S. R., D'Amore P. A. An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4544–4548. doi: 10.1073/pnas.86.12.4544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Antoszyk A. N., Gottlieb J. L., Machemer R., Hatchell D. L. The effects of intravitreal triamcinolone acetonide on experimental pre-retinal neovascularization. Graefes Arch Clin Exp Ophthalmol. 1993;231(1):34–40. doi: 10.1007/BF01681698. [DOI] [PubMed] [Google Scholar]
  9. Archer D. B., Gardiner T. A. Electron microscopic features of experimental choroidal neovascularization. Am J Ophthalmol. 1981 Apr;91(4):433–457. doi: 10.1016/0002-9394(81)90230-0. [DOI] [PubMed] [Google Scholar]
  10. Archer D. B., Gardiner T. A. Morphologic fluorescein angiographic, and light microscopic features of experimental choroidal neovascularization. Am J Ophthalmol. 1981 Mar;91(3):297–311. doi: 10.1016/0002-9394(81)90281-6. [DOI] [PubMed] [Google Scholar]
  11. Ausprunk D. H., Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res. 1977 Jul;14(1):53–65. doi: 10.1016/0026-2862(77)90141-8. [DOI] [PubMed] [Google Scholar]
  12. BenEzra D. Neovasculogenic ability of prostaglandins, growth factors, and synthetic chemoattractants. Am J Ophthalmol. 1978 Oct;86(4):455–461. doi: 10.1016/0002-9394(78)90289-1. [DOI] [PubMed] [Google Scholar]
  13. Breier G., Albrecht U., Sterrer S., Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 1992 Feb;114(2):521–532. doi: 10.1242/dev.114.2.521. [DOI] [PubMed] [Google Scholar]
  14. Chan-Ling T., Gock B., Stone J. The effect of oxygen on vasoformative cell division. Evidence that 'physiological hypoxia' is the stimulus for normal retinal vasculogenesis. Invest Ophthalmol Vis Sci. 1995 Jun;36(7):1201–1214. [PubMed] [Google Scholar]
  15. D'Amato R. J., Loughnan M. S., Flynn E., Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082–4085. doi: 10.1073/pnas.91.9.4082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. D'Amore P. A., Glaser B. M., Brunson S. K., Fenselau A. H. Angiogenic activity from bovine retina: partial purification and characterization. Proc Natl Acad Sci U S A. 1981 May;78(5):3068–3072. doi: 10.1073/pnas.78.5.3068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Danis R. P., Yang Y., Massicotte S. J., Boldt H. C. Preretinal and optic nerve head neovascularization induced by photodynamic venous thrombosis in domestic pigs. Arch Ophthalmol. 1993 Apr;111(4):539–543. doi: 10.1001/archopht.1993.01090040131047. [DOI] [PubMed] [Google Scholar]
  18. Dobi E. T., Puliafito C. A., Destro M. A new model of experimental choroidal neovascularization in the rat. Arch Ophthalmol. 1989 Feb;107(2):264–269. doi: 10.1001/archopht.1989.01070010270035. [DOI] [PubMed] [Google Scholar]
  19. Dorey C. K., Aouididi S., Reynaud X., Dvorak H. F., Brown L. F. Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat. Arch Ophthalmol. 1996 Oct;114(10):1210–1217. doi: 10.1001/archopht.1996.01100140410008. [DOI] [PubMed] [Google Scholar]
  20. Ferris F. L., 3rd, Fine S. L., Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984 Nov;102(11):1640–1642. doi: 10.1001/archopht.1984.01040031330019. [DOI] [PubMed] [Google Scholar]
  21. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  22. Fournier G. A., Lutty G. A., Watt S., Fenselau A., Patz A. A corneal micropocket assay for angiogenesis in the rat eye. Invest Ophthalmol Vis Sci. 1981 Aug;21(2):351–354. [PubMed] [Google Scholar]
  23. Freund K. B., Yannuzzi L. A., Sorenson J. A. Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol. 1993 Jun 15;115(6):786–791. doi: 10.1016/s0002-9394(14)73649-9. [DOI] [PubMed] [Google Scholar]
  24. Hamilton A. M., Kohner E. M., Rosen D., Bird A. C., Dollery C. T. Experimental retinal branch vein occlusion in rhesus monkeys. I. Clinical appearances. Br J Ophthalmol. 1979 Jun;63(6):377–387. doi: 10.1136/bjo.63.6.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hamilton A. M., Marshall J., Kohner E. M., Bowbyes J. A. Retinal new vessel formation following experimental vein occlusion. Exp Eye Res. 1975 Jun;20(6):493–497. doi: 10.1016/0014-4835(75)90216-x. [DOI] [PubMed] [Google Scholar]
  26. Hockley D. J., Tripathi R. C., Ashton N. Experimental retinal branch vein occlusion in the monkey. Histopathological and ultrastructural studies. Trans Ophthalmol Soc U K. 1976 Jul;96(2):202–209. [PubMed] [Google Scholar]
  27. Houck K. A., Ferrara N., Winer J., Cachianes G., Li B., Leung D. W. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991 Dec;5(12):1806–1814. doi: 10.1210/mend-5-12-1806. [DOI] [PubMed] [Google Scholar]
  28. Houck K. A., Leung D. W., Rowland A. M., Winer J., Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem. 1992 Dec 25;267(36):26031–26037. [PubMed] [Google Scholar]
  29. Husain D., Miller J. W., Michaud N., Connolly E., Flotte T. J., Gragoudas E. S. Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization. Arch Ophthalmol. 1996 Aug;114(8):978–985. doi: 10.1001/archopht.1996.01100140186012. [DOI] [PubMed] [Google Scholar]
  30. Keck P. J., Hauser S. D., Krivi G., Sanzo K., Warren T., Feder J., Connolly D. T. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989 Dec 8;246(4935):1309–1312. doi: 10.1126/science.2479987. [DOI] [PubMed] [Google Scholar]
  31. Kimura H., Sakamoto T., Hinton D. R., Spee C., Ogura Y., Tabata Y., Ikada Y., Ryan S. J. A new model of subretinal neovascularization in the rabbit. Invest Ophthalmol Vis Sci. 1995 Sep;36(10):2110–2119. [PubMed] [Google Scholar]
  32. Klein R., Klein B. E., Jensen S. C., Meuer S. M. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997 Jan;104(1):7–21. doi: 10.1016/s0161-6420(97)30368-6. [DOI] [PubMed] [Google Scholar]
  33. Kohner E. M., Dollery C. T., Shakib M., Henkind P., Paterson J. W., De Oliveira L. N., Bulpitt C. J. Experimental retinal branch vein occlusion. Am J Ophthalmol. 1970 May;69(5):778–825. doi: 10.1016/0002-9394(70)93420-3. [DOI] [PubMed] [Google Scholar]
  34. Kramer M., Miller J. W., Michaud N., Moulton R. S., Hasan T., Flotte T. J., Gragoudas E. S. Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys. Ophthalmology. 1996 Mar;103(3):427–438. doi: 10.1016/s0161-6420(96)30675-1. [DOI] [PubMed] [Google Scholar]
  35. Kvanta A., Algvere P. V., Berglin L., Seregard S. Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1996 Aug;37(9):1929–1934. [PubMed] [Google Scholar]
  36. Leung D. W., Cachianes G., Kuang W. J., Goeddel D. V., Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989 Dec 8;246(4935):1306–1309. doi: 10.1126/science.2479986. [DOI] [PubMed] [Google Scholar]
  37. Li W. W., Grayson G., Folkman J., D'Amore P. A. Sustained-release endotoxin. A model for inducing corneal neovascularization. Invest Ophthalmol Vis Sci. 1991 Oct;32(11):2906–2911. [PubMed] [Google Scholar]
  38. Little H. L., Rosenthal A. R., Dellaporta A., Jacobson D. R. The effect of pan-retinal photo-coagulation on rubeosis iridis. Am J Ophthalmol. 1976 Jun;81(6):804–809. doi: 10.1016/0002-9394(76)90364-0. [DOI] [PubMed] [Google Scholar]
  39. Lopez P. F., Sippy B. D., Lambert H. M., Thach A. B., Hinton D. R. Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1996 Apr;37(5):855–868. [PubMed] [Google Scholar]
  40. Lutty G. A., McLeod D. S., Merges C., Diggs A., Plouét J. Localization of vascular endothelial growth factor in human retina and choroid. Arch Ophthalmol. 1996 Aug;114(8):971–977. doi: 10.1001/archopht.1996.01100140179011. [DOI] [PubMed] [Google Scholar]
  41. Maione T. E., Gray G. S., Petro J., Hunt A. J., Donner A. L., Bauer S. I., Carson H. F., Sharpe R. J. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science. 1990 Jan 5;247(4938):77–79. doi: 10.1126/science.1688470. [DOI] [PubMed] [Google Scholar]
  42. Malecaze F., Clamens S., Simorre-Pinatel V., Mathis A., Chollet P., Favard C., Bayard F., Plouet J. Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol. 1994 Nov;112(11):1476–1482. doi: 10.1001/archopht.1994.01090230090028. [DOI] [PubMed] [Google Scholar]
  43. McLeod D. S., Crone S. N., Lutty G. A. Vasoproliferation in the neonatal dog model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1322–1333. [PubMed] [Google Scholar]
  44. Millauer B., Wizigmann-Voos S., Schnürch H., Martinez R., Møller N. P., Risau W., Ullrich A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 1993 Mar 26;72(6):835–846. doi: 10.1016/0092-8674(93)90573-9. [DOI] [PubMed] [Google Scholar]
  45. Miller H., Miller B., Ishibashi T., Ryan S. J. Pathogenesis of laser-induced choroidal subretinal neovascularization. Invest Ophthalmol Vis Sci. 1990 May;31(5):899–908. [PubMed] [Google Scholar]
  46. Miller H., Miller B. Photodynamic therapy of subretinal neovascularization in the monkey eye. Arch Ophthalmol. 1993 Jun;111(6):855–860. doi: 10.1001/archopht.1993.01090060145039. [DOI] [PubMed] [Google Scholar]
  47. Miller H., Miller B., Ryan S. J. The role of retinal pigment epithelium in the involution of subretinal neovascularization. Invest Ophthalmol Vis Sci. 1986 Nov;27(11):1644–1652. [PubMed] [Google Scholar]
  48. Miller J. W., Adamis A. P., Aiello L. P. Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diabetes Metab Rev. 1997 Mar;13(1):37–50. doi: 10.1002/(sici)1099-0895(199703)13:1<37::aid-dmr174>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  49. Miller J. W., Adamis A. P., Shima D. T., D'Amore P. A., Moulton R. S., O'Reilly M. S., Folkman J., Dvorak H. F., Brown L. F., Berse B. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol. 1994 Sep;145(3):574–584. [PMC free article] [PubMed] [Google Scholar]
  50. Miller J. W., Stinson W. G., Folkman J. Regression of experimental iris neovascularization with systemic alpha-interferon. Ophthalmology. 1993 Jan;100(1):9–14. doi: 10.1016/s0161-6420(93)31712-4. [DOI] [PubMed] [Google Scholar]
  51. Miller J. W., Stinson W. G., Gregory W. A., el-Koumy H. A., Puliafito C. A. Phthalocyanine photodynamic therapy of experimental iris neovascularization. Ophthalmology. 1991 Nov;98(11):1711–1719. doi: 10.1016/s0161-6420(91)32079-7. [DOI] [PubMed] [Google Scholar]
  52. Miller J. W., Walsh A. W., Kramer M., Hasan T., Michaud N., Flotte T. J., Haimovici R., Gragoudas E. S. Photodynamic therapy of experimental choroidal neovascularization using lipoprotein-delivered benzoporphyrin. Arch Ophthalmol. 1995 Jun;113(6):810–818. doi: 10.1001/archopht.1995.01100060136048. [DOI] [PubMed] [Google Scholar]
  53. Moses M. A., Sudhalter J., Langer R. Identification of an inhibitor of neovascularization from cartilage. Science. 1990 Jun 15;248(4961):1408–1410. doi: 10.1126/science.1694043. [DOI] [PubMed] [Google Scholar]
  54. Muthukkaruppan V., Auerbach R. Angiogenesis in the mouse cornea. Science. 1979 Sep 28;205(4413):1416–1418. doi: 10.1126/science.472760. [DOI] [PubMed] [Google Scholar]
  55. Nork T. M., Tso M. O., Duvall J., Hayreh S. S. Cellular mechanisms of iris neovascularization secondary to retinal vein occlusion. Arch Ophthalmol. 1989 Apr;107(4):581–586. doi: 10.1001/archopht.1989.01070010595037. [DOI] [PubMed] [Google Scholar]
  56. PATZ A. Oxygen studies in retrolental fibroplasia. IV. Clinical and experimental observations. Am J Ophthalmol. 1954 Sep;38(3):291–308. doi: 10.1016/0002-9394(54)90845-4. [DOI] [PubMed] [Google Scholar]
  57. Packer A. J., Gu X. Q., Servais E. G., Hayreh S. S. Primate model of neovascular glaucoma. Int Ophthalmol. 1986 May;9(2-3):121–127. doi: 10.1007/BF00159840. [DOI] [PubMed] [Google Scholar]
  58. Packer A. J., Tse D. T., Gu X. Q., Hayreh S. S. Hematoporphyrin photoradiation therapy for iris neovascularization. A preliminary report. Arch Ophthalmol. 1984 Aug;102(8):1193–1197. doi: 10.1001/archopht.1984.01040030971028. [DOI] [PubMed] [Google Scholar]
  59. Pattengale P. K., Stewart T. A., Leder A., Sinn E., Muller W., Tepler I., Schmidt E., Leder P. Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. Am J Pathol. 1989 Jul;135(1):39–61. [PMC free article] [PubMed] [Google Scholar]
  60. Pe'er J., Shweiki D., Itin A., Hemo I., Gnessin H., Keshet E. Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab Invest. 1995 Jun;72(6):638–645. [PubMed] [Google Scholar]
  61. Penn J. S., Tolman B. L., Lowery L. A. Variable oxygen exposure causes preretinal neovascularization in the newborn rat. Invest Ophthalmol Vis Sci. 1993 Mar;34(3):576–585. [PubMed] [Google Scholar]
  62. Pierce E. A., Avery R. L., Foley E. D., Aiello L. P., Smith L. E. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):905–909. doi: 10.1073/pnas.92.3.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Plouët J., Schilling J., Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J. 1989 Dec 1;8(12):3801–3806. doi: 10.1002/j.1460-2075.1989.tb08557.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Pournaras C. J., Tsacopoulos M., Strommer K., Gilodi N., Leuenberger P. M. Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy. Ophthalmology. 1990 Oct;97(10):1321–1328. doi: 10.1016/s0161-6420(90)32415-6. [DOI] [PubMed] [Google Scholar]
  65. Reynaud X., Dorey C. K. Extraretinal neovascularization induced by hypoxic episodes in the neonatal rat. Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3169–3177. [PubMed] [Google Scholar]
  66. Robinson G. S., Pierce E. A., Rook S. L., Foley E., Webb R., Smith L. E. Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4851–4856. doi: 10.1073/pnas.93.10.4851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Ryan S. J. Subretinal neovascularization after argon laser photocoagulation. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1980;215(1):29–42. doi: 10.1007/BF00413394. [DOI] [PubMed] [Google Scholar]
  68. Ryan S. J. Subretinal neovascularization. Natural history of an experimental model. Arch Ophthalmol. 1982 Nov;100(11):1804–1809. doi: 10.1001/archopht.1982.01030040784015. [DOI] [PubMed] [Google Scholar]
  69. Sakamoto T., Soriano D., Nassaralla J., Murphy T. L., Oganesian A., Spee C., Hinton D. R., Ryan S. J. Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate. Arch Ophthalmol. 1995 Feb;113(2):222–226. doi: 10.1001/archopht.1995.01100020106040. [DOI] [PubMed] [Google Scholar]
  70. Senger D. R., Galli S. J., Dvorak A. M., Perruzzi C. A., Harvey V. S., Dvorak H. F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983–985. doi: 10.1126/science.6823562. [DOI] [PubMed] [Google Scholar]
  71. Shima D. T., Adamis A. P., Ferrara N., Yeo K. T., Yeo T. K., Allende R., Folkman J., D'Amore P. A. Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med. 1995 Jan;1(2):182–193. [PMC free article] [PubMed] [Google Scholar]
  72. Shima D. T., Gougos A., Miller J. W., Tolentino M., Robinson G., Adamis A. P., D'Amore P. A. Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of Macaca fascicularis. Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1334–1340. [PubMed] [Google Scholar]
  73. Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992 Oct 29;359(6398):843–845. doi: 10.1038/359843a0. [DOI] [PubMed] [Google Scholar]
  74. Smith L. E., Wesolowski E., McLellan A., Kostyk S. K., D'Amato R., Sullivan R., D'Amore P. A. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994 Jan;35(1):101–111. [PubMed] [Google Scholar]
  75. Stone J., Chan-Ling T., Pe'er J., Itin A., Gnessin H., Keshet E. Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 1996 Feb;37(2):290–299. [PubMed] [Google Scholar]
  76. Tano Y., Chandler D. B., Machemer R. Retinal neovascularization after intravitreal fibroblast injection. Am J Ophthalmol. 1981 Jul;92(1):103–109. doi: 10.1016/s0002-9394(14)75913-6. [DOI] [PubMed] [Google Scholar]
  77. Tobe T., Takahashi K., Ohkuma H., Uyama M. [Experimental choroidal neovascularization in the rat]. Nippon Ganka Gakkai Zasshi. 1994 Sep;98(9):837–845. [PubMed] [Google Scholar]
  78. Tolentino M. J., Miller J. W., Gragoudas E. S., Chatzistefanou K., Ferrara N., Adamis A. P. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Arch Ophthalmol. 1996 Aug;114(8):964–970. doi: 10.1001/archopht.1996.01100140172010. [DOI] [PubMed] [Google Scholar]
  79. Tolentino M. J., Miller J. W., Gragoudas E. S., Jakobiec F. A., Flynn E., Chatzistefanou K., Ferrara N., Adamis A. P. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology. 1996 Nov;103(11):1820–1828. doi: 10.1016/s0161-6420(96)30420-x. [DOI] [PubMed] [Google Scholar]
  80. Virdi P. S., Hayreh S. S. Ocular neovascularization with retinal vascular occlusion. I. Association with experimental retinal vein occlusion. Arch Ophthalmol. 1982 Feb;100(2):331–341. doi: 10.1001/archopht.1982.01030030333024. [DOI] [PubMed] [Google Scholar]
  81. Wand M., Dueker D. K., Aiello L. M., Grant W. M. Effects of panretinal photocoagulation on rubeosis iridis, angle neovascularization, and neovascular glaucoma. Am J Ophthalmol. 1978 Sep;86(3):332–339. doi: 10.1016/0002-9394(78)90235-0. [DOI] [PubMed] [Google Scholar]
  82. Zack D. J., Bennett J., Wang Y., Davenport C., Klaunberg B., Gearhart J., Nathans J. Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas. Neuron. 1991 Feb;6(2):187–199. doi: 10.1016/0896-6273(91)90355-4. [DOI] [PubMed] [Google Scholar]
  83. Zhu Z. R., Goodnight R., Sorgente N., Ogden T. E., Ryan S. J. Experimental subretinal neovascularization in the rabbit. Graefes Arch Clin Exp Ophthalmol. 1989;227(3):257–262. doi: 10.1007/BF02172759. [DOI] [PubMed] [Google Scholar]
  84. elDirini A. A., Ogden T. E., Ryan S. J. Subretinal endophotocoagulation. A new model of subretinal neovascularization in the rabbit. Retina. 1991;11(2):244–249. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES