Oxidative stress in age-related macular degeneration: NRF2 as therapeutic target

Age-related macular degeneration is one of the leading causes of vision loss in the elderly. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease. All these risk factors are linked to the induction of oxidative stress. In young subjects retinal pigment epithelial cells mitigate reactive oxygen generation by the elimination of dysfunctional mitochondria, via mitophagy, and by increasing antioxidant defenses via Nrf2 activation. The high amount of UV light absorbed by the retina, together with cigarette smoking, cooperate with the aging process to increase the amount of reactive oxygen species generated by retinal pigment epithelium where oxidative stress arises. Moreover, in the elderly both the mitophagic process and Nrf2 activation are impaired thus causing retinal cell death. This review will focus on the impact of oxidative stress on the pathogenesis of age-related macular degeneration and analyze the natural and synthetic Nrf2-activating compounds that have been tested as potential therapeutic agents for the disease.