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

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
• melatonin
• mitochondria
• oxidative stress
• autophagy
• apoptosis

Article Highlights

• Mitochondrial dysfunction plays an important role in the pathogenesis of AMD.

• Mitochondrial bioenergetics decline during aging because of the insufficient free radical scavenger systems, impairment of DNA repair mechanisms and reduction of mitochondrial degradation and turnover.

• Oxidative/nitrosative stress plays an important role in the AMD development.

• Mitochondria are the major sites for melatonin synthesis and metabolism.

• Melatonin-specific receptors have been detected in different cell types of retina.

• The serum level of melatonin is reduced in AMD patients.

• Melatonin can reduce oxidative stress, inflammation and apoptosis in the retina and thus has the potential to prevent and treat AMD.

Declaration of Interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.