GLIAL REACTIVITY AND IMPAIRED GLUTAMATE METABOLISM IN SHORT-TERM EXPERIMENTAL DIABETIC-RETINOPATHY

The early pathophysiology of diabetic retinopathy and the involvement of neural and vascular malfunction are poorly understood. Glial cells provide structural and metabolic support for retinal neurons and blood vessels, and the cells become reactive in certain injury states, We t herefore used the streptozotocin rat model of short-term diabetic reti nopathy to study glial reactivity and other glial functions in the ret ina in the first months after onset of diabetes. With a two-site enzym e-linked immunosorbent assay, we measured the expression of the interm ediate filament glial fibrillary acidic protein (GFAP). After 1 month, GFAP was largely unchanged, but within 3 months of the beginning of d iabetes, it was markedly induced, by fivefold (P < 0.04). Immunohistoc hemical staining showed that the GFAP induction occurred both in astro cytes and in Muller cells. Consistent with a glial cell malfunction, t he ability of retinas to convert glutamate into glutamine, assayed chr omatographically with an isotopic method, was reduced in diabetic rats to 65% of controls (P <0.01). Furthermore, retinal glutamate, as dete rmined by luminometry, increased by 1.6-fold (P < 0.04) after 3 months of diabetes. Taken together, these findings indicate that glial react ivity and altered glial glutamate metabolism are early pathogenic even ts that may lead to elevated retinal glutamate during diabetes. These data are the first demonstration of a specific defect in glial cell me tabolism in the retina during diabetes. These findings suggest a novel understanding of the mechanism of neural degeneration in the retina d uring diabetes, involving early and possibly persistent glutamate exci totoxicity.