Effect of Pigment Epithelium Derived Factor on the Expression of Glutamine Synthetase in Early Phase of Experimental Diabetic Retinopathy

Purpose: A predominant function of Muller cells is to regulate glutamate levels, but in diabetic retinopathy (DR) the function is compromised. The present study was performed to investigate the role of pigment epithelial-derived factor (PEDF) on the expression of glutamine synthetase (GS) in retina of diabetic rats. Methods: The levels of interleukin-1 ss (IL-1 ss), PEDF, and GS in the retina of diabetic rats were analyzed by Western blotting and real-time-RT-PCR, and glutamate concentrations in retina or vitreous body were determined by high-pressure liquid chromatography. After being treated with PEDF in diabetic rats, these proteins (IL-1 ss and GS) and their mRNAs, as well as glutamate concentrations, were detected. To confirm the effect of PEDF on GS against the role of IL-1 ss, treatments with IL-1 ss companied with or without PEDF were performed in the eyes of normal rats. Results: Diabetes increased IL-1 ss levels and decreased PEDF and GS levels in retina. Simultaneously, diabetes induced elevated glutamate concentrations in retina and vitreous body. Administration of PEDF ameliorated the characteristic changes in diabetic retinopathy. Moreover, the effect of IL-1 ss on the expression of GS was inhibited by PEDF in retina of normal rats. Conclusions: PEDF increases expression of GS against the effect of IL-1 ss in early diabetic retinopathy. These findings suggest that PEDF may act as an anti-inflammatory factor against decrease of GS expression in retinal Muuller cells in diabetic retinopathy.