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Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 3528274, 13 pages
Research Article

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

1Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China
2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China
3Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX 77555, USA

Received 9 December 2015; Revised 14 March 2016; Accepted 17 March 2016

Academic Editor: Francisco J. Romero

Copyright © 2016 Tingting Jiang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.