Autophagy and Age-Related Eye Diseases

Abstract

Background. Autophagy is a catabolic process that depends on the lysosome. It is usually used to maintain cellular homeostasis, survival and development by degrading abnormal substances and dysfunctional organelles, especially when the cell is exposed to starvation or other stresses. Increasing studies have reported that autophagy is associated with various eye diseases, of which aging is one of the important factors. Objective. To summarize the functional and regulatory role of autophagy in ocular diseases with aging, and discuss the possibility of autophagy-targeted therapy in age-related diseases. Methods. PubMed searches were performed to identify relevant articles published mostly in the last 5 years. The key words were used to retrieve including “autophagy”, “aging”, “oxidative stress AND autophagy”, “dry eye AND autophagy”, “corneal disease AND autophagy”, “glaucoma AND autophagy”, “cataract AND autophagy”, “AMD AND autophagy”, “cardiovascular diseases AND autophagy”, “diabetes AND autophagy”. After being classified and assessed, the most relevant full texts in English were chosen. Results. Apart from review articles, more than two research articles for each age-related eye diseases related to autophagy were retrieved. We only included the most relevant and recent studies for summary and discussion. Conclusion. Autophagy has both protective and detrimental effects on the progress of age-related eye diseases. Different types of studies based on certain situations in vitro showed distinct results, which do not necessarily coincide with the actual situation in human bodies completely. It means the exact role and regulatory function of autophagy in ocular diseases remains largely unknown. Although autophagy as a potential therapeutic target has been proposed, many problems still need to be solved before it applies to clinical practice.

Quercetin Alleviates the Accumulation of Superoxide in Sodium Iodate-Induced Retinal Autophagy by Regulating Mitochondrial Reactive Oxygen Species Homeostasis through Enhanced Deacetyl-SOD2 via the Nrf2-PGC-1α-Sirt1 Pathway

“…Autophagy is an intracellular recycling process that regulates cellular homeostasis, such as RPE cells [38,47]. However, the autophagy activity was decreased in the AMD disease, which is caused by the oxidative damage originating from the dysfunction of RPE cells [21]. Therefore, the study tried to use quercetin, a potential antioxidant substrate, to investigate the protective efficacy on the mice with retinal oxidative damage, and demonstrated the detailed mechanism in the ARPE19 cell line.…”

“…It has been demonstrated that ROS generation can induce autophagy [18,19]. Autophagy has been reported to be involved in the oxidative responses of age-related eye diseases [21]. An increased level of oxidative stress has been shown to contribute to various autophagy-associated proteins, such as Beclin-1, Bcl-2, LC3B, and p62 [38,42].…”

“…However, autophagy plays a dual role in ophthalmic diseases. The activation of autophagy can reduce oxidative stress to preserve intracellular homeostasis, whereas the overactivation of autophagy can cause cell death [20,21].…”

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

“…Overall, an impairment of autophagy due to oxidative stress is related with several age-related eye diseases such as dry eye diseases, corneal dystrophy type 2, cataracts and retinal dystrophies like AMD, glaucoma, DR, and retinal artery occlusion [51,52].…”

Acute ultraviolet A exposure induces autophagy in RPE cells

“…Impairment of autophagy has been shown to contribute to many diseases [27]. Autophagy has both positive and negative effects on the progress of AMD [28]. Autophagy can be modulated by UVA in the skin [29,30], but whether UVA leads to AMD through regulating autophagy processes in RPE cells has not been elucidated.…”