The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates

5 April 2023

Archives Italiennes de Biologie – A Journal of Neuroscience – 2023

Increasing findings indicate that a dysfunction in the autophagy machinery is common during retinal degeneration. The present article provides evidence showing that an autophagy defect in the outer retinal layers is commonly described at the onset of retinal degeneration. These findings involve a number of structures placed at the border between the inner choroid and the outer retina encompassing the choriocapillaris, the Bruch’s membrane, photoreceptors and Mueller cells. At the center of these anatomical substrates are placed cells forming the retinal pigment epithelium (RPE), where autophagy seems to play most of its effects. In fact, a failure of the autophagy flux is mostly severe at the level of RPE. Among various retinal degenerative disorders, age-related macular degeneration (AMD) is mostly affected by a damage to RPE, which can be reproduced by inhibiting the autophagy machinery and it can be counteracted by the activation of the autophagy pathway. In the present manuscript evidence is provided that such a severe impairment of retinal autophagy may be counteracted by administration of a number of phytochemicals, which possess a strong stimulatory activity on autophagy. Likewise, natural light stimulation administered in the form of pulsatile specific wavelengths is capable of inducing autophagy within the retina. This dual approach to stimulate autophagy is further strengthened by the interaction of light with phytochemicals which is shown to activate the chemical properties of these natural molecules in sustaining retinal integrity. The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.