title: Poly (ADP-ribose) polymerase mediates diabetes-induced retinal neuropathy.
abstract: 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.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, P.O. Box 245, Riyadh 11411, Saudi Arabia.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, P.O. Box 245, Riyadh 11411, Saudi Arabia.
authors.forename: Mohammad Mairaj
authors.initials: MM
authors.lastname: Siddiquei
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, P.O. Box 245, Riyadh 11411, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000209:etiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D007546:Isoquinolines; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin
chemical_list: D000098:Acetophenones; D019208:Brain-Derived Neurotrophic Factor; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011804:Quinolines; D017382:Reactive Oxygen Species; C095653:1,5-dihydroxyisoquinoline; D013311:Streptozocin; C056165:acetovanillone; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D005974:Glutamate-Ammonia Ligase