Aier School of Ophthalmology, Central South University, Aier Eye Institute, Changsha 410015, Hunan Province, China.
Department of Ophthalmology, Aier Eye Hospital of Changsha, Changsha 410015, Hunan Province, China.
Biomed Res Int. 2020 Feb 13;2020:3862509. doi: 10.1155/2020/3862509. eCollection 2020.
Diabetic retinopathy (DR) is a sight-threatening complication of diabetes. This study investigated the therapeutic effect of probucol in a mouse model of diabetic retinopathy. C57BL/6 mice were rendered diabetic through Streptozotocin (STZ) intraperitoneal injection. Mice were treated with probucol (150 mg/kg, gavage administration) or vehicle (DMSO) for 12 weeks. Optical coherence tomography (OCT), fundus photography (FP), and fundus fluorescein angiography (FFA) were conducted to evaluate retinal structure and damage. Eyes were collected for histology, reactive oxygen species (ROS) assay, apoptotic cells count, and western blot. After STZ injection, all mice developed hyperglycemia. Compared with the retina of the control group, the retina of diabetic mice showed enhanced arterial reflex and beaded vein dilatation. Besides, reduced inner and middle retinal thickness and significantly fewer nuclei were found in diabetic retina. Moreover, the diabetic retina also presented increased ROS generation and more TUNEL-positive cells. Probucol treatment prevented diabetes-induced lesions. In addition, the treatment also upregulated Nrf2 expression in diabetic retina. It was suggested that probucol attenuated diabetes-induced retinal neuronal degeneration via upregulating the Nrf2 signaling pathway possibly. Probucol may be repurposed for DR management.
糖尿病性视网膜病变（DR）是糖尿病致盲的严重并发症。本研究探讨了普罗布考在糖尿病性视网膜病变小鼠模型中的治疗效果。通过腹腔注射链脲佐菌素（STZ）使 C57BL/6 小鼠发生糖尿病。用普罗布考（150mg/kg，灌胃给药）或载体（DMSO）处理小鼠 12 周。采用光学相干断层扫描（OCT）、眼底照相（FP）和眼底荧光血管造影（FFA）评估视网膜结构和损伤。收集眼球进行组织学、活性氧（ROS）测定、凋亡细胞计数和 Western blot。STZ 注射后，所有小鼠均出现高血糖。与对照组相比，糖尿病小鼠的视网膜表现出增强的动脉反射和珠状静脉扩张。此外，糖尿病视网膜还表现出内、中层视网膜厚度降低，细胞核明显减少。此外，糖尿病视网膜还表现出 ROS 生成增加和更多的 TUNEL 阳性细胞。普罗布考治疗可预防糖尿病引起的损伤。此外，该治疗还上调了糖尿病视网膜中的 Nrf2 表达。提示普罗布考可能通过上调 Nrf2 信号通路减轻糖尿病诱导的视网膜神经元变性。普罗布考可能被重新用于 DR 的治疗。
