Anti-inflammatory α-Melanocyte-Stimulating Hormone Protects Retina After Ischemia/Reperfusion Injury in Type I Diabetes.
Anti-inflammatory α-Melanocyte-Stimulating Hormone Protects Retina After Ischemia/Reperfusion Injury in Type I Diabetes.
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DOI：
10.3389/fnins.2022.799739
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发表时间：
2022
影响因子：
4.3
通讯作者：
Lo ACY
中科院分区：
文献类型：
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作者：
Goit RK;Taylor AW;Lo ACY
视网膜缺血/再灌注（I/R）损伤是许多眼部疾病中视力丧失的主要原因。视网膜I/R损伤在糖尿病视网膜病变中是常见的，其作为高血糖症的结果损害视网膜，并且如果不治疗可导致失明。炎症是I/R损伤发病机制中的主要促成因素。α-促黑素细胞激素（α-Melanocyte-stimulating hormone，α-MSH）是一种抗炎肽类激素，对I/R诱导的器官损伤具有保护作用。本研究采用高血糖C57 BL/6 J Ins 2 Akita/+小鼠，探讨α-MSH对I/R诱导的糖尿病视网膜损伤的保护作用。实验性I/R损伤通过阻断右侧大脑中动脉（MCA）2 h，然后使用管腔内方法再灌注2 h或22 h来诱导。由于眼动脉起源于MCA起源的近端，因此细丝也阻断了视网膜的血液供应。在缺血后1h和再灌注后1h给予α-MSH治疗后，动物在视网膜电图中显示出b波和振荡电位的振幅显著改善。α-MSH还能防止I/R诱导的组织学改变，抑制视网膜肿胀的发展。视网膜神经节细胞的丢失以及氧化应激在α-MSH处理的视网膜中显著减弱。α-MSH治疗后IL-10水平明显升高。此外，α-MSH给药后谷氨酸天冬氨酸转运体1、单羧酸转运体（MCT）1和MCT-2的基因表达显著升高。总之，α-MSH减轻了高血糖条件下I/R诱导的视网膜损伤的严重程度。α-MSH的这些有益作用可能对高血糖条件下视网膜I/R损伤具有重要的治疗意义。
Retinal ischemia/reperfusion (I/R) injury is a major cause of vision loss in many ocular diseases. Retinal I/R injury is common in diabetic retinopathy, which as a result of hyperglycemia damages the retina and can cause blindness if left untreated. Inflammation is a major contributing factor in the pathogenesis of I/R injury. α-Melanocyte-stimulating hormone (α-MSH) is an anti-inflammatory peptide hormone that has displayed protective effects against I/R-induced organ damages. Here, we aimed to investigate the protective role of α-MSH on I/R-induced diabetic retinal damage using hyperglycemic C57BL/6J Ins2Akita/+ mice. Experimental I/R injury was induced by blocking the right middle cerebral artery (MCA) for 2 h followed by 2 h or 22 h of reperfusion using the intraluminal method. Since ophthalmic artery originates proximal to the origin of the MCA, the filament also blocked blood supply to the retina. Upon treatment with α-MSH at 1 h after ischemia and 1 h after reperfusion, animals displayed significant improvement in amplitudes of b-wave and oscillatory potentials during electroretinography. α-MSH also prevented I/R-induced histological alterations and inhibited the development of retinal swelling. Loss of retinal ganglion cells as well as oxidative stress were significantly attenuated in the α-MSH-treated retinae. Level of interleukin 10 was significantly increased after α-MSH treatment. Moreover, gene expression of glutamate aspartate transporter 1, monocarboxylate transporter (MCT) 1 and MCT-2 were significantly higher after α-MSH administration. In conclusion, α-MSH mitigates the severity of I/R-induced retinal damage under hyperglycemic condition. These beneficial effects of α-MSH may have important therapeutic implications against retinal I/R injury under hyperglycemic condition.
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影响因子：
5.3
作者：
Allen, Rachael S.;Sayeed, Iqbal;Cale, Heather A.;Morrison, Katherine C.;Boatright, Jeffrey H.;Pardue, Machelle T.;Stein, Donald G.
通讯作者：
Stein, Donald G.
影响因子：
40.5
作者：
Antonetti, David A.;Silva, Paolo S.;Stitt, Alan W.
通讯作者：
Stitt, Alan W.
影响因子：
3.4
作者：
Garcia JM;Stillings SA;Leclerc JL;Phillips H;Edwards NJ;Robicsek SA;Hoh BL;Blackburn S;Doré S
通讯作者：
Doré S
影响因子：
3.8
作者：
HOLDEMAN, M;LIPTON, JM
通讯作者：
LIPTON, JM
影响因子：
82.9
作者：
通讯作者：
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