EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN THE HUMAN RETINA AND IN NONPROLIFERATIVE DIABETIC-RETINOPATHY

Vascular endothelial growth factor (VEGF)/vascular permeability factor is a likely angiogenic mediator in proliferative diabetic retinopathy , and its role is under scrutiny in the pathogenesis of the capillary leakage characteristic of background diabetic retinopathy. To examine whether the diabetic milieu induces or increases retinal VEGF expressi on in humans, we examined retinas from nondiabetic eye donors and dono rs with 9 +/- 5 years of diabetes and documented microangiopathy. To i dentify possible confounding effects of the postmortem period, we also studied the postmortem stability of the VEGF transcript and the expre ssion of the VEGF protein in rat retinas. In both human and rat retina we detected by Northern analysis a 4.2-kb VEGF mRNA species and by re verse transcriptase polymerase chain reaction the transcripts encoding VEGF(165) (the most abundant), VEGF(121), and VEGF(189). By in situ h ybridization and immunohistochemistry VEGF mRNA and protein co-localiz ed at the ganglion cell, inner nuclear, and outer plexiform layers and in the walls of the blood vessels (where mRNA was scarce). The protei n was additionally detected in photoreceptors. The abundance and distr ibution of VEGF mRNA and protein were not altered in the diabetic reti nas, indicating that the diabetic environment is not sufficient to inc rease retinal VEGF expression. The demonstration that VEGF is constitu tively expressed in the adult retina and is localized to discrete neur al cells and their processes proposes a role for the cytokine in retin al homeostasis and/or function.