Department of Ophthalmology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
Brain Res. 2025 Jan 1;1846:149253. doi: 10.1016/j.brainres.2024.149253. Epub 2024 Sep 25.
Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines its major pathological process. However, current treatments have limited efficacy and may even cause serious complications. Remote ischemic conditioning (RIC), through repeated transient mechanical occlusion of limb blood vessels, has been confirmed to promote blood-brain barrier integrity after stroke, but its role in BRB disruption has not been elucidated. This study aimed to investigate the protective effects of RIC on the BRB in diabetic rats and its potential mechanisms. 48 Sprague-Dawley rats were randomly assigned to the Sham group, Sham + RIC group, diabetes mellitus (DM) group and DM+RIC group. The diabetic model was successfully induced by intraperitoneal injection of streptozotocin. RIC treatment was administered daily and lasted for 9 weeks. In functional analysis, RIC improved the retinal function based on electroretinogram data and reduced the leakage of BRB in diabetic rats. In proteomic analysis, tight junction pathway was enriched after RIC treatment, in which Patj gene was significantly increased. We also found that RIC increased mRNA levels of Patj, claudin-1 and zonula occludens (ZO)-1, protein expression of claudin-1 when compared with diabetic models. In conclusion, RIC slowed BRB damage in diabetic rats, which may be related to the preservation of tight junction proteins. RIC may be a promising protective strategy for the treatment of DR.
糖尿病性视网膜病变(DR)是糖尿病的主要并发症之一,可导致严重的视力损害。慢性高血糖引起的血视网膜屏障(BRB)破坏是其主要的病理过程。然而,目前的治疗方法疗效有限,甚至可能导致严重的并发症。远程缺血预处理(RIC)通过反复短暂地阻断肢体血管血流,已被证实可促进中风后的血脑屏障完整性,但它在 BRB 破坏中的作用尚未阐明。本研究旨在探讨 RIC 对糖尿病大鼠 BRB 的保护作用及其潜在机制。48 只 Sprague-Dawley 大鼠随机分为假手术组、假手术+RIC 组、糖尿病组和糖尿病+RIC 组。通过腹腔注射链脲佐菌素成功诱导糖尿病模型。RIC 治疗每天进行,持续 9 周。在功能分析中,RIC 改善了基于视网膜电图数据的视网膜功能,并减少了糖尿病大鼠 BRB 的渗漏。在蛋白质组学分析中,RIC 处理后紧密连接通路被富集,其中 Patj 基因显著增加。我们还发现,与糖尿病模型相比,RIC 增加了 Patj、claudin-1 和 zonula occludens (ZO)-1 的 mRNA 水平,以及 claudin-1 的蛋白表达。总之,RIC 减缓了糖尿病大鼠的 BRB 损伤,这可能与紧密连接蛋白的保存有关。RIC 可能是治疗 DR 的一种有前途的保护策略。