Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina

Abstract

Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has shown that autophagy proteins are involved in retinal physiology and pathology and that defective autophagy contributes to retinal degeneration. In retinal diseases, autophagy plays a dual role: promoting retinal cell survival and death. Autophagy at a normal level helps retinal cells defend themselves against harmful stress; however, excessive autophagy results in retinal deterioration. Both synergistic and antagonistic roles of autophagy and apoptosis in the retina have been reported in the literature. In this review, we summarize the roles of autophagy in the development of the retina and retinal diseases. This review highlights the importance of autophagy in retinal diseases, and targeting autophagy may provide a new therapeutic approach for retinal diseases.

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

“…Autophagy is another lysosome-mediated degradation process essential for maintaining cellular homeostasis [265]. Autophagic flux, the complete dynamic process of autophagy, includes multiple steps involving the formation of phagosomes and autophagosomes, autophagosome fusion with lysosomes, the degradation of the intra-autophagosomal contents, and recycling [266].…”

“…High basal autophagic levels are maintained in RPE and PR cells. RPE cells being post-mitotic phagocytes are not self-renewing; the autophagy of intracellular components is therefore essential for a normal cellular function of the RPE [265]. In PR cells, autophagy occurs during various cellular activities such as OS degeneration [269], rhodopsin protein expression [270], visual cycle function, and PR apoptosis [271].…”

The urokinase‐type plasminogen activator system as drug target in retinitis pigmentosa: New pre‐clinical evidence in the rd10 mouse model

“…UPARANT was found to reduce the Bax/Bcl2 ratio and active caspase 3 levels by approximately 2.9‐ and 1.3‐fold, respectively ( P < 0.001). In retinal cell degeneration, autophagy is a conserved cellular self‐degradation process that not only plays a major role by serving as cell survival mechanism, but also contributes to cell death . In rd10 mice, we analysed the lipidation of the autophagosomal marker LC3 and we found that levels of the lipidated form of LC3 (LC3 II) were decreased, whereas those of the autophagy substrate p62 were increased (representative blots in Figure D and uncropped blots in Figure ).…”

“…In retinal cell degeneration, autophagy is a conserved cellular self-degradation process that not only plays a major role by serving as cell survival mechanism, but also contributes to cell death. 32 In rd10 mice, we analysed the lipidation of the autophagosomal marker LC3 and we found that levels of the lipidated form of LC3 (LC3 II) were decreased, whereas those of the autophagy substrate p62 were increased (representative blots in Figure 2D and uncropped blots in Figure S1). Densitometric analysis (Figure 2E,F) demonstrates that, in respect to control WT mice, in rd10 mice, LC3 II levels were decreased and p62 levels were increased by approximately 2.5-and 1.8-fold, respectively (P < 0.001).…”

Selective Histone Deacetylase 6 Inhibitors Restore Cone Photoreceptor Vision or Outer Segment Morphology in Zebrafish and Mouse Models of Retinal Blindness

“…However, other studies report autophagy is increased as a mechanism to clear out mutant proteins or damaged cells or as a response to oxidative stress (Kaushal, 2006;Kunchithapautham and Rohrer, 2007;Bogea et al, 2015). Hence, a balance is required in autophagy in diseased conditions to ensure a beneficial effect (Moreno et al, 2018;Lin and Xu, 2019).…”