Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity

Western diet-induced obesity is linked to the development of metabolic dysfunctions, including type 2 diabetes and complications that include retinopathy, a leading cause of blindness. Aberrant activation of the inflammasome cascade leads to the progression of obesity-induced pathologies. Our lab sh...

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Veröffentlicht in:Journal of clinical medicine 2020-01, Vol.9 (2), p.317
Hauptverfasser: Atawia, Reem T, Bunch, Katharine L, Fouda, Abdelrahman Y, Lemtalsi, Tahira, Eldahshan, Wael, Xu, Zhimin, Saul, Alan, Elmasry, Khaled, Al-Shabrawey, Mohamed, Caldwell, Ruth B, Caldwell, R William
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container_issue 2
container_start_page 317
container_title Journal of clinical medicine
container_volume 9
creator Atawia, Reem T
Bunch, Katharine L
Fouda, Abdelrahman Y
Lemtalsi, Tahira
Eldahshan, Wael
Xu, Zhimin
Saul, Alan
Elmasry, Khaled
Al-Shabrawey, Mohamed
Caldwell, Ruth B
Caldwell, R William
description Western diet-induced obesity is linked to the development of metabolic dysfunctions, including type 2 diabetes and complications that include retinopathy, a leading cause of blindness. Aberrant activation of the inflammasome cascade leads to the progression of obesity-induced pathologies. Our lab showed the critical role of arginase 2 (A2), the mitochondrial isoform of this ureahydrolase, in obesity-induced metabolic dysfunction and inflammation. A2 deletion also has been shown to be protective against retinal inflammation in models of ischemic retinopathy and multiple sclerosis. We investigated the effect of A2 deletion on western diet-induced retinopathy. Wild-type mice fed a high-fat, high-sucrose western diet for 16 weeks exhibited elevated retinal expression of A2, markers of the inflammasome pathway, oxidative stress, and activation of microglia/macrophages. Western diet feeding induced exaggerated retinal light responses without affecting visual acuity or retinal morphology. These effects were reduced or absent in mice with global A2 deletion. Exposure of retinal endothelial cells to palmitate and high glucose, a mimic of the obese state, increased expression of A2 and inflammatory mediators and induced cell death. These effects, except for A2, were prevented by pretreatment with an arginase inhibitor. Collectively, our study demonstrated a substantial role of A2 in early manifestations of diabetic retinopathy.
doi_str_mv 10.3390/jcm9020317
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source PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Animals
Antibodies
Clinical medicine
Cytokines
Diabetes
Diabetic retinopathy
Diet
Glucose
Inflammation
Laboratories
Metabolism
Nitric oxide
Obesity
Oxidative stress
Proteins
Retina
Sucrose
title Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
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