Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa

每日补充褪黑激素对视网膜色素变性啮齿动物模型中视力丧失、昼夜节律和肝脏氧化损伤的影响

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作者:Lorena Fuentes-Broto, Lorena Perdices, Francisco Segura, Elvira Orduna-Hospital, Gema Insa-Sánchez, Ana I Sánchez-Cano, Nicolás Cuenca, Isabel Pinilla

Abstract

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by a progressive loss of visual function that primarily affect photoreceptors, resulting in the complete disorganization and remodeling of the retina. Progression of the disease is enhanced by increased oxidative stress in the retina, aqueous humor, plasma, and liver of RP animal models and patients. Melatonin has beneficial effects against age-related macular degeneration, glaucoma, and diabetic retinopathy, in which oxidative stress plays a key role. In the present study, we used the P23HxLE rat as an animal model of RP. Melatonin treatment (10 mg/kg b.w. daily in drinking water for 6 months) improved the parameters of visual function and decreased the rate of desynchronization of the circadian rhythm, both in P23HxLE and wild-type rats. Melatonin reduced oxidative stress and increased antioxidant defenses in P23HxLE animals. In wild-type animals, melatonin did not modify any of the oxidative stress markers analyzed and reduced the levels of total antioxidant defenses. Treatment with melatonin improved visual function, circadian synchronization, and hepatic oxidative stress in P23HxLE rats, an RP model, and had beneficial effects against age-related visual damage in wild-type rats.

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