Mitochondria: Potential Targets for Protection in Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in older adults in developed countries. The molecular mechanisms of disease pathogenesis remain poorly understood; however, evidence suggests that mitochondrial dysfunction may contribute to the progression of the disease. Studies have shown that mitochondrial DNA lesions are increased in the retinal pigment epithelium (RPE) of human patients with the disease and that the number of these lesions increases with disease severity. Additionally, microscopy of human RPE from patients with dry AMD shows severe disruptions in mitochondrial inner and outer membrane structure, mitochondrial size, and mitochondrial cellular organization. Thus, improving our understanding of mitochondrial dysfunction in dry AMD pathogenesis may lead to the development of targeted therapies. We propose that mitochondrial dysfunction in the RPE can lead to the chronic oxidative stress associated with the disease. Therefore, one protective strategy may involve the use of small molecule therapies that target the regulation of mitochondrial biogenesis and mitochondrial fission and mitophagy.