Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy.
OBJECTIVE
To determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which have been implicated in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes before proliferative retinopathy appears.


METHODS
Light microscopic immunocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen sections from eyes 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 vascular digest preparations to evaluate microvascular abnormalities.


RESULTS
Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells. Glial cells within septa surrounding axons in the anterior optic nerve also immunostained 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 than did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast growth factor was expressed minimally in the inner retinal layers of subjects with and without diabetes, but it was substantial in the photoreceptor layer of all eyes. Vascular endothelial growth factor immunopositivity was present in eyes with no, or little, retinal vascular anatomic abnormality in digest preparations.


CONCLUSIONS
Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes. Its localization to glial cells of the inner retina and the anterior optic nerve suggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retinal nonperfusion and little likelihood of retinal neovascularization suggests the possibility that ischemia may not be the sole stimulus for VEGF expression.
Amin
R H
RH
Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Frank
R N
RN
Kennedy
A
A
Eliott
D
D
Puklin
J E
JE
Abrams
G W
GW
D000368:Aged; D000369:Aged, 80 and over; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014746:Vimentin / Q000378:metabolism
D016228:Endothelial Growth Factors; D005904:Glial Fibrillary Acidic Protein; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014746:Vimentin; D016222:Fibroblast Growth Factor 2; D005169:Factor VIII