Upregulation of Vascular Endothelial Growth Factor (VEGF) and its receptors in non-ischemic retinal disease

S. A. Vinores, Y. S. Chen, D. A. Klein, M. A. Vinores, C. C. Chan, W. R. Green, Peter A Campochiaro

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Abstract

Purpose: VEGF is induced by hypoxia and promotes neovascularization in ischemic disease, but it is also known to be a potent mediator of vascular permeability. The present study was conducted to determine if upregulation ot VEGF or its receptors is associated with blood-retinal barrier (BRB) breakdown in the absence of neovasculariztition in non-ischemic ocular disease. Methods: Paraffin sections of eyes from 36 Lewis rats immunized with S-antigen to induce experimental autoimmune uveoretinitis (EAU), from 20 spontaneously diabetic BB/Wistar rats, and from 164 human eyes with a variety of ocular disorders as well as the appropriate controls were immunohistochemically stained for VEGF or its receptors, flt or flk-1. and evaluated in a blind study. To insure that the immunohistochemical staining was specific, primary antibodies were pre-incubated with peptide controls. Results: Normal rat and human retinas were negative for VEGF and flk-1, but some positivity for flt was seen, particularly in the inner retina. In S-antigen immunized rats, VEGF and its receptors were upregulated in the inner retina prior to the development of EAU. In diabetic rats and in a variety of clinical specimens of ischemic and non-ischemic disorders, VEGF was significantly increased in the retina and RPE. Flk-1 was rarely seen in human specimens, but flt staining appeared more intense throughout the retina in certain disorders, particularly Bechet's disease, which like EAU appears to involve an autoimmune reaction to S-antigen. Immunohistochemical staining was eliminated by pre-incubation of the primary antibody with the purified antigen. Conclusions: VEGF is known to be associated will neovascularization in ischemic retinopathies, but VEGF also appears to play a role in a number of ocular disorders in which ischemia or neovascularization does not appear to be a primary pathological feature. It is likely that VEGF may potentiate blood-retinal barrier breakdown in these instances or it may mediate as yet unrecognised functions.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
Publication statusPublished - Feb 15 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Ophthalmology

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