VASCULAR ENDOTHELIAL GROWTH-FACTOR IS PRESENT IN GLIAL-CELLS OF THE RETINA AND OPTIC-NERVE OF HUMAN-SUBJECTS WITH NONPROLIFERATIVE DIABETIC-RETINOPATHY

Purpose. To determine whether vascular endothelial growth factor (VEGF ) and basic fibroblast growth factor (bFGF), which have been implicate d in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes befo re proliferative retinopathy appears. Methods. Light microscopic immun ocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrill ary acidic protein (GFAP), and factor VIII on frozen sections from eye s of patients with diabetes without proliferative retinopathy, eyes of patients without diabetes and without known ocular disease, and eyes with disciform age-related macular degeneration (ARMD). Retinal vascul ar digest preparations to evaluate microvascular abnormalities. Result s. Based on morphology and on GFAP and vimentin immunopositivity, reti nas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Miller cells. Glial cells with in septa surrounding axons in the anterior optic nerve also immunostai ned for VEGF, as did endothelial cells of some posterior retinal blood vessels and some retinal pigment epithelial cells. Retinas from eyes with disciform ARMD immunostained for VEGF, though less extensively th an did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast g rowth factor was expressed minimally in the inner retinal layers of su bjects with and without diabetes, but it was substantial in the photor eceptor layer of all eyes. Vascular endothelial growth factor immunopo sitivity was present in eyes with no, or little, retinal vascular anat omic abnormality in digest preparations. Conclusions. Vascular endothe lial growth factor expression precedes retinal neovascularization in t he retinas and the optic nerves of humans with diabetes. Its localizat ion to glial cells of the inner retina and the anterior optic nerve su ggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retin al nonperfusion and little likelihood of retinal neovascularization su ggests the possibility that ischemia may not be the sole stimulus for VEGF expression