Upregulation of Glutamate–Aspartate Transporter by Glial Cell Line–Derived Neurotrophic Factor Ameliorates Cell Apoptosis in Neural Retina in Streptozotocin‐Induced Diabetic Rats

Abstract

Dysfunction of glutamate uptake, largely mediated by the glutamate-aspartate transporter (GLAST), may lead to retinal cell apoptosis in diabetic retinopathy. The aim of this study is to examine how cell apoptosis and the expression level of GLAST in neural retina of a diabetic rat model are changed and whether the neuroretinal apoptosis could be ameliorated by the administration of glial cell line-derived neurotrophic factor (GDNF). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. GLAST protein expression levels were determined by Western blotting, whereas apoptosis of retinal neurons was evaluated by TUNEL staining. To assess the role of GDNF in ameliorating the STZ-induced retinal changes, GDNF/GDNF with siRNA directed against GLAST was injected into the vitreous after STZ injection. In rat retinas 4weeks after the onset of STZ-induced diabetes, TUNEL-positive cells were significantly increased, whereas GLAST levels were significantly reduced. Intraocular administration of GDNF at the early stage of diabetes remarkably increased the GLAST levels and decreased TUNEL-positive signals in the retinas. These effects of GDNF were largely abolished by coadministration of GLAST siRNA. GDNF, administrated at the early stage of diabetes, could rescue retinal cells from neurodegeneration by upregulating the expression of GLAST.