VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ITS RECEPTORS IN CONTROL AND DIABETIC RAT EYES

Vascular endothelial growth factor (VEGF) is an endothelial cell-speci fic angiogenic and permeability-inducing factor that has been implicat ed in the pathogenesis of diabetic retinopathy. In the present study, the localization and magnitude of VEGF, VEGF receptor-1 (VEGFR-1), and VEGF receptor-2 (VEGFR-2) gene expression were examined in the eye of streptozotocin-induced diabetic rats using quantitative in situ hybri dization. VEGF protein was also examined by immunohistochemistry. Abun dant VEGF mRNA and protein were present in the retinae of control rats . In the retinae of diabetic rats, VEGF gene expression was increased compared with control animals (p = 0.001). The increase in VEGF mRNA w as noted in the ganglion cell layer and inner nuclear layer but not in the pigment epithelium of the retina. VEGF was also detected in blood vessels, ciliary body, and lens epithelium in both control and diabet ic rats. The distributions of VEGFR-1 and VEGFR-2 were similar in both control and diabetic rats. VEGFR-1 mRNA was present beneath the inner limiting membrane and in the ganglion cell layer, inner nuclear layer , outer plexiform layer, and outer limiting membrane of the retina; it was also detected in blood vessels, the ciliary body, and the cornea. The magnitude and distribution of ocular VEGFR-1 mRNA were not affect ed by experimental diabetes. Expression of VEGFR-2 mRNA was noted in t he inner nuclear layer and pigment epithelium of the retina and in blo od vessels. An increase in VEGFR-2 mRNA in the diabetic retina was res tricted to the inner nuclear layer. The presence of VEGF and its recep tors in the control retina suggests a physiologic role for VEGF within the eye. The changes in retinal expression of VEGF and VEGFR-2 in ass ociation with diabetes suggest a role for this pathway in diabetic ret inopathy.