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Magnesium acetyltaurate protects against endothelin-1 induced RGC loss by reducing neuroinflammation in Sprague dawley rats.
Experimental Eye Research ( IF 3.4 ) Pub Date : 2020-03-07 , DOI: 10.1016/j.exer.2020.107996
Natasha Najwa Nor Arfuzir 1 , Renu Agarwal 2 , Igor Iezhitsa 3 , Puneet Agarwal 2 , Nafeeza Mohd Ismail 2
Affiliation  

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.

中文翻译:

乙酰牛磺酸镁可通过减少Sprague dawley大鼠的神经炎症来防止内皮素1诱导的RGC丢失。

内皮素-1(ET-1)是一种有效的血管收缩剂,在青光眼等眼部疾病的病理生理中起着重要作用。青光眼的特征在于视网膜神经节细胞(RGC)的凋亡消失和视野丧失,并且是不可逆性失明的主要原因。在青光眼中,视网膜缺血会导致促炎性介质(如白介素(IL)-1β,IL-6和肿瘤坏死因子(TNF)-α)释放,并促进转录因子(如核因子κB(NFKB)和c君 先前已显示乙酰牛磺酸镁(MgAT)可防止ET-1引起的视网膜和视神经损伤。当前的研究调查了MgAT的这些作用的潜在机制,至今仍未知。玻璃体腔注射ET-1的Sprague dawley大鼠,无论是否接受MgAT预处理。注射后7天,使用多重测定,蛋白质印迹和PCR确定IL-1β,IL-6,TNF-α,NFKB和c-Jun蛋白和基因的视网膜表达。对动物进行RGC的逆行标记以确定RGC存活的程度。还使用Brn3A染色检查了RGC的存活率。此外,使用莫里斯水迷宫确定大鼠的视觉功能。观察到,用MgAT预处理可防止ET-1诱导的IL-1β,IL-6和TNF-α蛋白质和基因的视网膜表达增加。它还可以防止ET-1诱导的NFKB和c-Jun活化。MgAT的这些作用与大鼠更大的RGC存活和视觉功能的保持有关。结论,
更新日期:2020-03-09
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