Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration

The seminal role of autophagy during retinal degeneration grounds on the clearance of a 22 number of oxidative chemical species, which alter proteins and lipids structure and generate dys- 23 functional mitochondria. In fact, reactive oxidative species (ROS) in the retina generate misfolded 24 proteins, alter lipids and sugars composition, disrupt DNA integrity, damage cell organelles, and 25 produce retinal inclusions, while causing retinal degeneration. This explains why autophagy in the 26 retinal pigment epithelium (RPE), mostly at macular level, is very active, even in baseline condi- 27 tions, to provide a powerful and fast replacement of oxidized molecules and ROS-damaged mito- 28 chondria. 29 When autophagy is impaired within RPE, the deleterious effects of ROS, which derives also from 30 baseline conditions, are no longer counteracted and retinal degeneration may occur. Within RPE 31 autophagy can be induced by various stimuli, such as light and naturally occurring phytochemicals. 32 Light and phytochemicals in turn, may synergize to enhance autophagy since phytochemicals are 33 activated by light exposure. This may explain the beneficial effects of light pulses combined with 34 light-sensitive phytochemicals, for retinal structure, visual acuity preventing oxidative damage dur- 35 ing retinal degeneration. In this way, photo-sensitive natural compounds may produce light-de- 36 pendent beneficial antioxidant effects.