The Essential Role of Light-Induced Autophagy in the Inner Choroid/Outer Retinal Neurovascular Unit in Baseline Conditions and Degeneration

Abstract

The present article discusses the role of light in altering autophagy, both within the outer retina (retinal pigment epithelium, RPE, and the outer segment of photoreceptors) and the inner choroid (Bruch’s membrane, BM, endothelial cells and the pericytes of choriocapillaris, CC). Here autophagy is needed to maintain the high metabolic requirements and to provide the specific physiological activity sub-serving the process of vision. Activation or inhibition of autophagy within RPE strongly depends on light exposure and it is concomitant with activation or inhibition of the outer segment of the photoreceptors. This also recruits CC, which provides blood flow and metabolic substrates. Thus, the inner choroid and outer retina are mutually dependent and their activity is orchestrated by light exposure in order to cope with metabolic demand. This is tuned by the autophagy status, which works as a sort of pivot in the cross-talk within the inner choroid/outer retina neurovascular unit. In degenerative conditions, and mostly during age-related macular degeneration (AMD), autophagy dysfunction occurs in this area to induce cell loss and extracellular aggregates. Therefore, a detailed analysis of the autophagy status encompassing CC, RPE and interposed BM is key to understanding the fine anatomy and altered biochemistry which underlie the onset and progression of AMD.

Autophagy as a new player in the regulation of clock neurons physiology of Drosophila melanogaster

“…Interestingly, light seems to regulate autophagy in clock neurons, since in constant darkness the pattern of daily changes in early and late autophagosomes was different that in LD12:12 and autophagy flux was higher. However, we observed very low level of early autophagosomes in the lLNv terminals in the medulla of flies kept in constant darkness, which correlates with the data which showed that autophagy is light-driven in the retina 56 and may be enhanced by light in hippocampal cells in vitro 57 . This phenomenon needs more exploration in the future.…”