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Previous Volume 331:1480-1487 December 1, 1994 Number 22 Next

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ABSTRACT

Background Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia.

Methods We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody.

Results VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P<0.001, P<0.001, and P = 0.006, respectively). The mean (±SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 ±6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 ±0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 ±0.6 ng per milliliter, P<0.001), or 31 samples from nondiabetic patients (0.1 ±0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 ±9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 ±8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies.

Conclusions Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.

Source Information

From the Department of Ophthalmology, Beetham Eye Institute (L.P.A., P.G.A., S.T.S., L.M.A.), and the Division of Research (L.P.A., H.T., G.L.K.), Joslin Diabetes Center; the Departments of Medicine and Ophthalmology, Brigham and Women's Hospital (L.R.P., M.A.I., G.L.K.); and Harvard Medical School (L.P.A., P.G.A., S.T.S., L.R.P., H.T., M.A.I., L.M.A., G.L.K.) -- all in Boston; the Neuroscience Research Institute, University of California, Santa Barbara (R.L.A.); Genentech, Inc., San Francisco (B.A.K., J.E.P., H.V.N., N.F.); and the Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore (H.D.J.).

Address reprint requests to Dr. L.P. Aiello at the Beetham Eye Institute, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215.

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• The PKC-DRS Study Group, (2005). The Effect of Ruboxistaurin on Visual Loss in Patients With Moderately Severe to Very Severe Nonproliferative Diabetic Retinopathy: Initial Results of the Protein Kinase C {beta} Inhibitor Diabetic Retinopathy Study (PKC-DRS) Multicenter Randomized Clinical Trial. Diabetes 54: 2188-2197 [Abstract] [Full Text]  
• Mohan, J S, Lip, P L, Blann, A D, Bareford, D, Lip, G Y H (2005). The angiopoietin/Tie-2 system in proliferative sickle retinopathy: relation to vascular endothelial growth factor, its soluble receptor Flt-1 and von Willebrand factor, and to the effects of laser treatment. Br. J. Ophthalmol. 89: 815-819 [Abstract] [Full Text]  
• Yokoi, M, Yamagishi, S-i, Takeuchi, M, Ohgami, K, Okamoto, T, Saito, W, Muramatsu, M, Imaizumi, T, Ohno, S (2005). Elevations of AGE and vascular endothelial growth factor with decreased total antioxidant status in the vitreous fluid of diabetic patients with retinopathy. Br. J. Ophthalmol. 89: 673-675 [Abstract] [Full Text]  
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• Patel, J I, Hykin, P G, Gregor, Z J, Boulton, M, Cree, I A (2005). Angiopoietin concentrations in diabetic retinopathy. Br. J. Ophthalmol. 89: 480-483 [Abstract] [Full Text]  
• Simons, M. (2005). Angiogenesis: Where Do We Stand Now?. Circulation 111: 1556-1566 [Full Text]  
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• Yang, W. J., Yang, D. D., Na, S., Sandusky, G. E., Zhang, Q., Zhao, G. (2005). Dicer Is Required for Embryonic Angiogenesis during Mouse Development. J. Biol. Chem. 280: 9330-9335 [Abstract] [Full Text]  
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• Feliers, D., Duraisamy, S., Barnes, J. L., Ghosh-Choudhury, G., Kasinath, B. S. (2005). Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II. Am. J. Physiol. Renal Physiol. 288: F521-F529 [Abstract] [Full Text]  
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• Luttrull, J K, Musch, D C, Mainster, M A (2005). Subthreshold diode micropulse photocoagulation for the treatment of clinically significant diabetic macular oedema. Br. J. Ophthalmol. 89: 74-80 [Abstract] [Full Text]  
• Yamauchi, K., Nishimura, Y., Shigematsu, S., Takeuchi, Y., Nakamura, J., Aizawa, T., Hashizume, K. (2004). Vascular Endothelial Cell Growth Factor Attenuates Actions of Transforming Growth Factor-{beta} in Human Endothelial Cells. J. Biol. Chem. 279: 55104-55108 [Abstract] [Full Text]  
• Gragoudas, E. S., Adamis, A. P., Cunningham, E. T. Jr., Feinsod, M., Guyer, D. R., the VEGF Inhibition Study in Ocular Neovasculariza, (2004). Pegaptanib for Neovascular Age-Related Macular Degeneration. NEJM 351: 2805-2816 [Abstract] [Full Text]  
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• Savage, H. I., Hendrix, J. W., Peterson, D. C., Young, H., Wilkinson, C. P. (2004). Differences in Pulsatile Ocular Blood Flow among Three Classifications of Diabetic Retinopathy. IOVS 45: 4504-4509 [Abstract] [Full Text]  
• Hoeben, A., Landuyt, B., Highley, M. S., Wildiers, H., Van Oosterom, A. T., De Bruijn, E. A. (2004). Vascular Endothelial Growth Factor and Angiogenesis. Pharmacol. Rev. 56: 549-580 [Abstract] [Full Text]  
• Lip, P L, Chatterjee, S, Caine, G J, Hope-Ross, M, Gibson, J, Blann, A D, Lip, G Y H (2004). Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: effects of laser photocoagulation and angiotensin receptor blockade. Br. J. Ophthalmol. 88: 1543-1546 [Abstract] [Full Text]  
• Franklin, A. J., Jetton, T. L., Kuchemann, C. L., Russell, S. R., Kohn, E. C. (2004). CAI Is a Potent Inhibitor of Neovascularization and Imparts Neuroprotection in a Mouse Model of Ischemic Retinopathy. IOVS 45: 3756-3766 [Abstract] [Full Text]  
• Fong, D. S., Aiello, L. P., Ferris, F. L. III, Klein, R. (2004). Diabetic Retinopathy. Diabetes Care 27: 2540-2553 [Full Text]  
• Marano, R. J., Brankov, M., Rakoczy, P. E. (2004). Discovery of a Novel Control Element within the 5'-Untranslated Region of the Vascular Endothelial Growth Factor: REGULATION OF EXPRESSION USING SENSE OLIGONUCLEOTIDES. J. Biol. Chem. 279: 37808-37814 [Abstract] [Full Text]  
• Kondo, T., Kahn, C. R. (2004). Altered Insulin Signaling in Retinal Tissue in Diabetic States. J. Biol. Chem. 279: 37997-38006 [Abstract] [Full Text]  
• Ferrara, N. (2004). Vascular Endothelial Growth Factor: Basic Science and Clinical Progress. Endocr. Rev. 25: 581-611 [Abstract] [Full Text]  
• Menne, J., Park, J.-K., Boehne, M., Elger, M., Lindschau, C., Kirsch, T., Meier, M., Gueler, F., Fiebeler, A., Bahlmann, F. H., Leitges, M., Haller, H. (2004). Diminished Loss of Proteoglycans and Lack of Albuminuria in Protein Kinase C-{alpha}--Deficient Diabetic Mice. Diabetes 53: 2101-2109 [Abstract] [Full Text]  
• Poulaki, V., Joussen, A. M., Mitsiades, N., Mitsiades, C. S., Iliaki, E. F., Adamis, A. P. (2004). Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy. Am. J. Pathol. 165: 457-469 [Abstract] [Full Text]  
• Funatsu, H, Yamashita, H, Noma, H, Mimura, T, Sakata, K, Hori, S (2004). Risk evaluation of outcome of vitreous surgery for proliferative diabetic retinopathy based on vitreous level of vascular endothelial growth factor and angiotensin II. Br. J. Ophthalmol. 88: 1064-1068 [Abstract] [Full Text]  
• Duenas, Z., Rivera, J. C., Quiroz-Mercado, H., Aranda, J., Macotela, Y., de Oca, P. M., Lopez-Barrera, F., Nava, G., Guerrero, J. L., Suarez, A., De Regil, M., de la Escalera, G. M., Clapp, C. (2004). Prolactin in Eyes of Patients with Retinopathy of Prematurity: Implications for Vascular Regression. IOVS 45: 2049-2055 [Abstract] [Full Text]  
• Shie, J.-L., Wu, G., Wu, J., Liu, F.-F., Laham, R. J., Oettgen, P., Li, J. (2004). RTEF-1, a Novel Transcriptional Stimulator of Vascular Endothelial Growth Factor in Hypoxic Endothelial Cells. J. Biol. Chem. 279: 25010-25016 [Abstract] [Full Text]  
• Losordo, D. W., Dimmeler, S. (2004). Therapeutic Angiogenesis and Vasculogenesis for Ischemic Disease: Part II: Cell-Based Therapies. Circulation 109: 2692-2697 [Full Text]  
• Cooke, R. W. I., Drury, J. A., Mountford, R., Clark, D. (2004). Genetic Polymorphisms and Retinopathy of Prematurity. IOVS 45: 1712-1715 [Abstract] [Full Text]  
• Canton, A., Martinez-Caceres, E. M., Hernandez, C., Espejo, C., Garcia-Arumi, J., Simo, R. (2004). CD4-CD8 and CD28 Expression in T Cells Infiltrating the Vitreous Fluid in Patients With Proliferative Diabetic Retinopathy: A Flow Cytometric Analysis. Arch Ophthalmol 122: 743-749 [Abstract] [Full Text]  
• Sassa, Y., Hata, Y., Aiello, L. P., Taniguchi, Y., Kohno, K., Ishibashi, T. (2004). Bifunctional Properties of Peroxisome Proliferator-Activated Receptor {gamma}1 in KDR Gene Regulation Mediated via Interaction With Both Sp1 and Sp3. Diabetes 53: 1222-1229 [Abstract] [Full Text]  
• Miyahara, S., Kiryu, J., Yamashiro, K., Miyamoto, K., Hirose, F., Tamura, H., Katsuta, H., Nishijima, K., Tsujikawa, A., Honda, Y. (2004). Simvastatin Inhibits Leukocyte Accumulation and Vascular Permeability in the Retinas of Rats with Streptozotocin-Induced Diabetes. Am. J. Pathol. 164: 1697-1706 [Abstract] [Full Text]  
• Watanabe, D., Takagi, H., Suzuma, K., Suzuma, I., Oh, H., Ohashi, H., Kemmochi, S., Uemura, A., Ojima, T., Suganami, E., Miyamoto, N., Sato, Y., Honda, Y. (2004). Transcription Factor Ets-1 Mediates Ischemia- and Vascular Endothelial Growth Factor-Dependent Retinal Neovascularization. Am. J. Pathol. 164: 1827-1835 [Abstract] [Full Text]  
• Liu, H., Ren, J.-G., Cooper, W. L., Hawkins, C. E., Cowan, M. R., Tong, P. Y. (2004). Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. Proc. Natl. Acad. Sci. USA 101: 6605-6610 [Abstract] [Full Text]  
• Hinton, D. R., Spee, C., He, S., Weitz, S., Usinger, W., LaBree, L., Oliver, N., Lim, J. I. (2004). Accumulation of NH2-Terminal Fragment of Connective Tissue Growth Factor in the Vitreous of Patients With Proliferative Diabetic Retinopathy. Diabetes Care 27: 758-764 [Abstract] [Full Text]  
• Larger, E., Marre, M., Corvol, P., Gasc, J.-M. (2004). Hyperglycemia-Induced Defects in Angiogenesis in the Chicken Chorioallantoic Membrane Model. Diabetes 53: 752-761 [Abstract] [Full Text]  
• Ray, D., Mishra, M., Ralph, S., Read, I., Davies, R., Brenchley, P. (2004). Association of the VEGF Gene With Proliferative Diabetic Retinopathy But Not Proteinuria in Diabetes. Diabetes 53: 861-864 [Abstract] [Full Text]  
• Nguyen, Q. D., Shah, S. M., Van Anden, E., Sung, J. U., Vitale, S., Campochiaro, P. A. (2004). Supplemental Oxygen Improves Diabetic Macular Edema: A Pilot Study. IOVS 45: 617-624 [Abstract] [Full Text]