Raghu G, Akileshwari C, Reddy V Sudhakar, Reddy G Bhanuprakash
Biochemistry Division, National Institute of Nutrition, Tarnaka, Jamai-Osmania, Hyderabad, 500 007 India.
J Food Sci Technol. 2017 Jul;54(8):2411-2421. doi: 10.1007/s13197-017-2683-8. Epub 2017 May 29.
Diabetic retinopathy (DR) is a major concern for blindness all over the world. Diabetic retinopathy is associated with thickening of basement membrane, retinal thinning, retinal detachment, and pericyte death. Advanced glycation end products (AGEs) mediate the progression of DR by stimulating the expression of RAGE and VEGF which subsequently damages the blood-retinal barrier. Employing a set of in vitro protein glycation systems, earlier we demonstrated antiglycating potential of ellagic acid (EA). In this study, we evaluated the efficacy of EA to prevent in vivo accumulation of AGE and to ameliorate retinal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed either with 0.2 or 2% EA in the diet for 12 weeks. Effect of EA on retinal function was assessed with electroretinogram (ERG). At the end of the experiment, rats were scarified and retina was collected. Histology was carried out with H&E staining and immunohistochemistry. Formation of AGE product (CML) and activation of RAGE was analyzed by immunoblotting and immunohistochemistry. Expression of GFAP, VEGF, Bax and HIF-1α was assessed by qRT-PCR and immunoblotting. Dietary supplementation of EA to diabetic rats resulted in: (1) inhibition of accumulation of CML and activation of RAGE in retina, (2) attenuation of expression of GFAP, VEGF, and HIF-1α in retina, (3) attenuation of cell death by reducing proapoptic mediator Bax and (4) amelioration of retinal thickness and function. In conclusion, EA attenuated the retinal abnormalities including angiogenesis, hypoxia and cell death by inhibiting AGE-RAGE mediated cellular events.
糖尿病视网膜病变（DR）是全球失明的一个主要问题。糖尿病视网膜病变与基底膜增厚、视网膜变薄、视网膜脱离和周细胞死亡有关。晚期糖基化终产物（AGEs）通过刺激RAGE和VEGF的表达介导糖尿病视网膜病变的进展，进而损害血视网膜屏障。我们之前利用一组体外蛋白质糖基化系统证明了鞣花酸（EA）的抗糖基化潜力。在本研究中，我们评估了EA预防糖尿病大鼠体内AGE积累和改善视网膜变化的效果。将链脲佐菌素诱导的糖尿病大鼠分别用0.2%或2%的EA喂养12周。用电视网膜图（ERG）评估EA对视网膜功能的影响。实验结束时，处死大鼠并收集视网膜。进行苏木精-伊红（H&E）染色和免疫组织化学检查。通过免疫印迹和免疫组织化学分析AGE产物（CML）的形成和RAGE的激活。通过qRT-PCR和免疫印迹评估GFAP、VEGF、Bax和HIF-1α的表达。给糖尿病大鼠饮食中补充EA导致：（1）抑制视网膜中CML的积累和RAGE的激活，（2）减弱视网膜中GFAP、VEGF和HIF-1α的表达，（3）通过减少促凋亡介质Bax减轻细胞死亡，（4）改善视网膜厚度和功能。总之，EA通过抑制AGE-RAGE介导的细胞事件减轻了包括血管生成、缺氧和细胞死亡在内的视网膜异常。
