%0 Journal Article
%T Poly (ADP-Ribose) Polymerase Mediates Diabetes-Induced Retinal Neuropathy
%A Ghulam Mohammad
%A Mohammad Mairaj Siddiquei
%A Ahmed M. Abu El-Asrar
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/510451
%X Retinal neuropathy is an early event in the development of diabetic retinopathy. One of the potential enzymes that are activated by oxidative stress in the diabetic retina is poly (ADP-ribose) polymerase (PARP). We investigated the effect of the PARP inhibitor 1,5-isoquinolinediol on the expression of the neurodegeneration mediators and markers in the retinas of diabetic rats. After two weeks of streptozotocin-induced diabetes, rats were treated with 1,5-isoquinolinediol (3£¿mg/kg/day). After 4 weeks of diabetes, the retinas were harvested and the levels of reactive oxygen species (ROS) were determined fluorometrically and the expressions of PARP, phosporylated-ERK1/2, BDNF, synaptophysin, glutamine synthetase (GS), and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, PARP-1/2, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expressions of BDNF synaptophysin and GS were significantly decreased in the retinas of diabetic rats, compared to nondiabetic rats. Administration of 1,5-isoquinolinediol did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of PARP, ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF, synaptophysin, and GS. These findings suggest a beneficial effect of the PARP inhibitor in increasing neurotrophic support and ameliorating early retinal neuropathy induced by diabetes. 1. Introduction Diabetes is a metabolic disorder characterized by hyperglycemia and often leads to numerous microvascular complications, including retinopathy. Diabetic retinopathy (DR) is a multifactorial disease, and persistent hyperglycemia appears to be a major contributor to its development. Recent evidence suggests that diabetic retinopathy is a progressive neurodegenerative disease as evidenced by the presence of apoptotic cells in all retinal layers. Activation of caspase-3 is part of the mechanism of apoptosis. Visual dysfunction is initiated early after the onset of diabetes and progresses independently of the vascular lesions [1¨C4]. The exact molecular mechanisms which contribute to development of diabetes-induced retinal neuropathy remain largely unknown. Reactive oxygen species (ROS) production is increased in the retina in diabetes, and it is considered as one of the major contributors of retinal metabolic abnormalities postulated to be involved in the development of diabetic retinopathy. Administration of antioxidants to diabetic rats protects the retina from oxidative damage, and also the
%U http://www.hindawi.com/journals/mi/2013/510451/