Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models

Figure 2

The interrelationships between the molecular mechanisms involved in AMD show the potential therapeutic role of autophagy and Nrf2 activation in the disease. Oxidative damage to lipids, proteins, and DNA is seemingly the primary insult leading to age-related macular degeneration. The accumulation of lipids due to an inhibition of lipid metabolism promotes oxidative stress by increasing lipid peroxidation in the retina. Oxidative stress could initiate inflammation through the activation of the inflammasome, complement, and macrophages. Oxidative stress may also upregulate VEGF expression in the retina and induce choroidal neovascularization. The antioxidant mechanisms, including autophagy and Nrf2, which are upregulated under oxidative stress counteract further oxidative damage and maintain retinal homeostasis.