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JINGMING LI, GUO CHEN, FENGJUN ZHANG, GUOLONG DING, QIUPING LIU; Muller Cell-derived Paraoxonase 2 Reverses Vascular Dysfunction in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5196.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress through excessive generation of reactive oxygen species (ROS) is involved vascular leakage and degeneration in diabetic retinopathy (DR). Paraoxonase 2 (Pon2) plays a critical role in anti-oxidative defense. However, nothing is known about its role in retinas. The aim of this study is to elucidate Pon2’s function in regulating of retinal oxidative stress and vascular damage during DR.
A mouse model of diabetes was set up by intraperitoneal injection of streptozotocin. Retinal expression of Pon2 were determined by immunofluorescence. Induction of Pon2 in mouse retinas was achieved by intravitreal injection of AAV-PON2 or by feeding with Niacin. Retinal ROS generation, expression of vascular endothelial growth factor (VEGF), leukostasis, vascular leakage and formation of acellular capillaries were determined in by cellrox staining, western-blot analysis, Con A-lectin perfusion and trypsin digestion, respectively.
Retinal expression of Pon2 were increased in retinas of diabetic mice, which was mainly expressed by Muller cells. Retinal ROS generation and VEGF expression were significantly increased in diabetic mice, together with enhanced leukocytes adhesion to retinal vasculature, exacerbated vascular leakage and prominent acellular capillaries. Upregulation of AAV-PON2 markedly inhibited diabetes-induced retinal ROS generation and VEGF expression. In parallel, retinal leukostasis, vascular leakage and amount of acellular capillaries were dramatically reduced in diabetic mice with overexpression of Pon2.
Taken together, our data indicate that Pon2 plays a pivotal role in anti-oxidative defense in DR. Induction of Pon2 could be a potential therapeutic strategy of diabetic microvascular complications.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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