In the eye, the retina and surrounding tissues are exposed to one of the most highly oxidizing microenvironments in the entire human body. This is due, in part, to constant visible light exposure, elevated oxygen partial pressure and phagocytosis of the polyunsaturated fatty acid-loaded photoreceptor outer segments. Accordingly, numerous retinal degenerations including age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma are associated with oxidative stress. Oxidative damage and mitochondrial dysfunction are considered to be significant factors underlying the initiation and progression of cellular changes during aging and disease. This chapter discusses the high vulnerability of mitochondria and outlines current evidence implicating this organelle as a weak link in the retina. In particular, mitochondrial DNA (mtDNA) damage and defects in the mtDNA repair system may be particularly important to the pathogenesis retinal degenerations. We also consider the importance of mitochondrial biogenesis as well as removal of damaged mitochondria via autophagy as cellular strategies to minimize the effect of mitochondrial damage on cellular function. The specific targeting of mitochondria (e.g., biogenesis, removal, antioxidants, and DNA repair) with pharmacological agents able to protect against retinal damage may offer novel alternatives for the treatment of retinal degenerations.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)