Pigment epithelium derived factor as an anti-inflammatory factor against decrease of glutamine synthetase expression in retinal Müller cells under high glucose conditions

Abstract

The pathogenesis of diabetic retinopathy (DR) is similar to that of a chronic inflammatory disease. A predominant function of Müller cells is to regulate glutamate levels, but in 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 rat retinal Müller cells under high glucose conditions, and to study the possible mechanism for PEDF against decrease of GS expression in retinal Müller cells under high glucose conditions. The role of PEDF on the expressions of GS and interleukin-1beta (IL-1beta) in retinal Müller cells under normal and high glucose conditions was measured by western blotting, real-time RT-PCR, or immunocytochemistry. In order to confirm the effect of PEDF on GS against the role of IL-1beta, the PEDF siRNA method was used. High glucose increased the expression of IL-1beta, but decreased the expressions of GS and PEDF in retinal Müller cells. PEDF increased the expression of GS and decreased the expression of IL-1beta in retinal Müller cells under high glucose conditions. The effect of IL-1beta on expression of GS was inhibited by PEDF. Moreover, down-regulation of PEDF expression by siRNA resulted in significantly increasing the expression of IL-1beta, but decreasing the expression of GS in retinal Müller cells. PEDF increases expression of GS against the effect of IL-1beta in retinal Müller cells under high glucose conditions. These findings suggested that PEDF may act as an anti-inflammatory factor against decrease of GS expression in retinal Müller cells in diabetic retinopathy.