Loss of Response Gene to Complement 32 (RGC-32) in Diabetic Mouse Retina Is Involved in Retinopathy Development
Loss of Response Gene to Complement 32 (RGC-32) in Diabetic Mouse Retina Is Involved in Retinopathy Development
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DOI：
10.3390/ijms19113629
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发表时间：
2018-11-01
影响因子：
5.6
通讯作者：
Tsai, Fuu-Jen
中科院分区：
文献类型：
--
作者：
Liao, Wen-Ling;Lin, Jane-Ming;Tsai, Fuu-Jen
糖尿病视网膜病变(DR)是糖尿病中一种严重的、反复发生的微血管并发症。补体32的多功能反应基因(RGC-32)参与细胞周期、增殖和凋亡的调节。为了研究RGC-32在DR发生发展中的作用，我们使用了高糖条件下的人视网膜微血管内皮细胞和2型糖尿病(T2D)小鼠(+Lepr(Db)/+Lepr(Db)，db/db)。结果表明，在高血糖条件下，人视网膜内皮细胞RGC-32的表达呈中度升高。组织病理学和RGC-32的表达在16周龄和24周龄的T2D小鼠和对照组小鼠视网膜中没有明显变化。然而，32周龄的T2D小鼠视网膜RGC-32的表达显著低于对照组，表现出早期临床阶段DR的特征，即视网膜厚度减少和神经节细胞死亡增加。免疫组织化学显示，RGC-32主要在对照组小鼠光感受器内节段表达，而在T2D视网膜中的表达显著降低。此外，我们发现，与对照组相比，T2D视网膜中抗凋亡蛋白Bcl-2的水平降低(约2倍)，而caspase-3的裂解水平增加(约3倍)。综上所述，RGC-32可能在具有DR特征的T2D视网膜中失去表达，提示其在DR的发病机制中起关键作用。
Diabetic retinopathy (DR) is a severe and recurrent microvascular complication in diabetes. The multifunctional response gene to complement 32 (RGC-32) is involved in the regulation of cell cycle, proliferation, and apoptosis. To investigate the role of RGC-32 in the development of DR, we used human retinal microvascular endothelial cells under high-glucose conditions and type 2 diabetes (T2D) mice (+Lepr(db)/ + Lepr(db), db/db). The results showed that RGC-32 expression increased moderately in human retinal endothelial cells under hyperglycemic conditions. Histopathology and RGC-32 expression showed no significant changes between T2D and control mice retina at 16 and 24 weeks of age. However, RGC-32 expression was significantly decreased in T2D mouse retina compared to the control group at 32 weeks of age, which develop features of the early clinical stages of DR, namely reduced retinal thickness and increased ganglion cell death. Moreover, immunohistochemistry showed that RGC-32 was predominantly expressed in the photoreceptor inner segments of control mice, while the expression was dramatically lowered in the T2D retinas. Furthermore, we found that the level of anti-apoptotic protein Bcl-2 was decreased (approximately 2-fold) with a concomitant increase in cleaved caspase-3 (approximately 3-fold) in T2D retina compared to control. In summary, RGC-32 may lose its expression in T2D retina with features of DR, suggesting that it plays a critical role in DR pathogenesis.