Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment

Expert Opin Ther Targets. 2020 Apr;24(4):359-378. doi: 10.1080/14728222.2020.1737015. Epub 2020 Mar 2.

Abstract

Introduction: Age-related Macular Degeneration (AMD), a retinal neurodegenerative disease is the most common cause of blindness among the elderly in developed countries. The impairment of mitochondrial biogenesis has been reported in human retinal pigment epithelium (RPE) cells affected by AMD. Oxidative/nitrosative stress plays an important role in AMD development. The mitochondrial respiratory system is considered a major site of reactive oxygen species (ROS) generation. During aging, insufficient free radical scavenger systems, impairment of DNA repair mechanisms and reduction of mitochondrial degradation and turnover contribute to the massive accumulation of ROS disrupting mitochondrial function. Impaired mitochondrial function leads to the decline in the autophagic capacity and induction of inflammation and apoptosis in human RPE cells affected by AMD.Areas covered: This article evaluates the ameliorative effect of melatonin on AMD and examines AMD pathogenesis with an emphasis on mitochondrial dysfunction. It also considers the potential effects of melatonin on mitochondrial function.Expert opinion: The effect of melatonin on mitochondrial function results in the reduction of oxidative stress, inflammation and apoptosis in the retina; these findings demonstrate that melatonin has the potential to prevent and treat AMD.

Keywords: Age-related macular degeneration; apoptosis; autophagy; melatonin; mitochondria; oxidative stress.

Publication types

  • Review

MeSH terms

  • Aged
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Humans
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / physiopathology
  • Melatonin / administration & dosage
  • Melatonin / pharmacology*
  • Mitochondria / pathology*
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / pathology

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Melatonin