Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia.
School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
Exp Eye Res. 2020 May;194:107996. doi: 10.1016/j.exer.2020.107996. Epub 2020 Mar 7.
Endothelin-1 (ET-1), a potent vasoconstrictor, plays a significant role in the pathophysiology of ocular conditions like glaucoma. Glaucoma is characterized by apoptotic loss of retinal ganglion cells (RGCs) and loss of visual fields and is a leading cause of irreversible blindness. In glaucomatous eyes, retinal ischemia causes release of pro-inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and promotes activation of transcription factors such as nuclear factor kappa B (NFKB) and c-Jun. Magnesium acetyltaurate (MgAT) has previously been shown to protect against ET-1 induced retinal and optic nerve damage. Current study investigated the mechanisms underlying these effects of MgAT, which so far remain unknown. Sprague dawley rats were intravitreally injected with ET-1 with or without pretreatment with MgAT. Seven days post-injection, retinal expression of IL-1β, IL-6, TNF-α, NFKB and c-Jun protein and genes was determined using multiplex assay, Western blot and PCR. Animals were subjected to retrograde labeling of RGCs to determine the extent of RGC survival. RGC survival was also examined using Brn3A staining. Furthermore, visual functions of rats were determined using Morris water maze. It was observed that pre-treatment with MgAT protects against ET-1 induced increase in the retinal expression of IL-1β, IL-6 and TNF-α proteins and genes. It also protected against ET-1 induced activation of NFKB and c-Jun. These effects of MgAT were associated with greater RGC survival and preservation of visual functions in rats. In conclusion, MgAT prevents ET-1 induced RGC loss and loss of visual functions by suppressing neuroinflammatory reaction in rat retinas.
内皮素-1（ET-1）是一种强效的血管收缩剂，在青光眼等眼部疾病的病理生理学中发挥重要作用。青光眼的特征是视网膜神经节细胞（RGC）凋亡和视野丧失，是不可逆失明的主要原因。在青光眼眼中，视网膜缺血导致促炎介质如白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α的释放，并促进转录因子如核因子 kappa B（NFKB）和 c-Jun 的激活。先前已经表明，乙酰鸟氨酸镁（MgAT）可防止 ET-1 引起的视网膜和视神经损伤。目前的研究调查了 MgAT 产生这些作用的机制，但这些机制尚不清楚。将 ET-1 玻璃体腔内注射到 Sprague dawley 大鼠中，同时或不预先用 MgAT 处理。注射后 7 天，使用多重分析、Western blot 和 PCR 测定视网膜中 IL-1β、IL-6、TNF-α、NFKB 和 c-Jun 蛋白和基因的表达。通过逆行标记 RGC 来确定 RGC 存活的程度。还使用 Brn3A 染色检查 RGC 存活情况。此外，使用 Morris 水迷宫测定大鼠的视觉功能。结果观察到，MgAT 预处理可防止 ET-1 诱导的视网膜中 IL-1β、IL-6 和 TNF-α 蛋白和基因表达增加。它还可防止 ET-1 诱导的 NFKB 和 c-Jun 激活。MgAT 的这些作用与大鼠 RGC 存活增加和视觉功能保存有关。总之，MgAT 通过抑制大鼠视网膜中的神经炎症反应，防止 ET-1 诱导的 RGC 丢失和视觉功能丧失。
