Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy

• Published in: Oxidative medicine and cellular longevity Vol. 2016; no. 2016; pp. 1 - 13
• Main Authors: Zhang, Xiaozhe, Fan, Jiawen, Cai, Jiyang, Chang, Qing, Jiang, Tingting, Xu, Gezhi
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; Hindawi Limited
• Subjects: Animals; Antioxidants; Apoptosis; Cytokines; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Experiments; Inflammation; Kinases; Male; Melatonin - pharmacology; Melatonin - therapeutic use; Oxidative stress; Oxidative Stress - drug effects; Proteins; Rats; Rats, Sprague-Dawley; Retina; Rodents; Studies
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2016/3528274

Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.