α-Melanocyte-stimulating hormone reduces severity of retinal damage after retinal ischemia/reperfusion injury in type I diabetes

Abstract

Purpose : Retinal ischemia is a major cause of vision loss and a common feature of diabetic retinopathy (DR). This study hypothesized that α-Melanocyte-stimulating hormone (α-MSH) decreased severity of retinal damage after retinal ischemia/reperfusion (I/R) injury by downregulating oxidative stress and excitotoxicity while upregulating anti-inflammatory factor expression under hyperglycemia condition.

Methods : I/R injury was induced in type 1 diabetic C57BL/6J Ins2Akita/+ mice by blocking the middle cerebral artery (MCA) for 2 h with reperfusion for either 2 h or 22 h using the intraluminal method. Since ophthalmic artery originates proximal to the origin of the MCA, the filament also occluded blood flow to the retina. Animals were treated intraperitoneally with either vehicle or various doses of α-MSH at 1 h after ischemia and 1 h after reperfusion. Electroretinogram was recorded after dark adaptation. Paraformaldehyde-fixed eye sections were used to count ganglion cells, measure thickness of retinal layers and oxidative stress. Western blot was performed to measure anti-inflammatory factor expression and qPCR was performed to reflect excitotoxicity. Results : α-MSH significantly increased amplitudes of b-wave and oscillatory potentials (OPs). α-MSH also prevented the I/R-induced histological changes and the development of retinal swelling. Loss of retinal ganglion cells as well as poly-ADP-ribose immunoreactivity were significantly decreased in the α-MSH-treated group. Level of interleukin-10 was significantly increased after α-MSH treatment. In addition, gene expression of glutamate aspartate transporter 1, monocarboxylate transporter (MCT) 1 and MCT-2 were significantly higher in animals treated with α-MSH. Conclusions : α-MSH was associated with reduced severity of I/R induced retinal damage under hyperglycemic condition. In addition, increased amplitudes of b-wave and OPs were observed in animals treated with α-MSH. These beneficial effects of α-MSH may have important therapeutic implications against retinal I/R injury under hyperglycemic condition. This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.