Department of Ophthalmology, Ruijin Hospital, School of Medicine, The Jiaotong University, Shanghai, China.
Ocul Immunol Inflamm. 2011 Aug;19(4):246-54. doi: 10.3109/09273948.2011.580073.
A predominant function of Müller 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.
The levels of interleukin-1ß (IL-1ß), 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-1ß 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-1ß, treatments with IL-1ß companied with or without PEDF were performed in the eyes of normal rats.
Diabetes increased IL-1ß 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-1ß on the expression of GS was inhibited by PEDF in retina of normal rats.
PEDF increases expression of GS against the effect of IL-1ß in early diabetic retinopathy. These findings suggest that PEDF may act as an anti-inflammatory factor against decrease of GS expression in retinal Müller cells in diabetic retinopathy.
Müller 细胞的主要功能之一是调节谷氨酸水平，但在糖尿病视网膜病变（DR）中，其功能受损。本研究旨在探讨色素上皮衍生因子（PEDF）对糖尿病大鼠视网膜中谷氨酰胺合成酶（GS）表达的作用。
通过 Western blot 和实时 RT-PCR 分析糖尿病大鼠视网膜中白细胞介素-1β（IL-1β）、PEDF 和 GS 的水平，并通过高压液相色谱法测定视网膜或玻璃体中谷氨酸的浓度。在糖尿病大鼠中用 PEDF 处理后，检测这些蛋白质（IL-1β和 GS）及其 mRNA 以及谷氨酸浓度。为了确认 PEDF 对 GS 的作用是否对抗 IL-1β的作用，在正常大鼠的眼睛中进行了 IL-1β伴或不伴 PEDF 的处理。
糖尿病增加了视网膜中 IL-1β的水平，降低了 PEDF 和 GS 的水平。同时，糖尿病诱导了视网膜和玻璃体中谷氨酸浓度的升高。PEDF 的给药改善了糖尿病性视网膜病变的特征性变化。此外，IL-1β对 GS 表达的影响在正常大鼠的视网膜中被 PEDF 抑制。
在早期糖尿病性视网膜病变中，PEDF 通过增加 GS 的表达来对抗 IL-1β的作用。这些发现表明，PEDF 可能作为一种抗炎因子，对抗糖尿病性视网膜病变中视网膜 Müller 细胞中 GS 表达的减少。
