The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases

Abstract

Oxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which is highly associated with normal physiological homeostasis and the pathogenesis of diseases, particularly ocular diseases. Autophagy is a self-clearance pathway that removes oxidized cellular components and regulates cellular ROS levels. ROS can modulate autophagy activity through transcriptional and posttranslational mechanisms. Autophagy further triggers transcription factor activation and degrades impaired organelles and proteins to eliminate excessive ROS in cells. Thus, autophagy may play an antioxidant role in protecting ocular cells from oxidative stress. Nevertheless, excessive autophagy may cause autophagic cell death. In this review, we summarize the mechanisms of interaction between ROS and autophagy and their roles in the pathogenesis of several ocular diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and optic nerve atrophy, which are major causes of blindness. The autophagy modulators used to treat ocular diseases are further discussed. The findings of the studies reviewed here might shed light on the development and use of autophagy modulators for the future treatment of ocular diseases.

Diabetic Retinopathy: Role of Neurodegeneration and Therapeutic Perspectives

“…In contrast to rodents, zebrafish have a cone-dominated retina and develop neovascularization. These characteristics, combined with their short lifespan, rapid growth, and ability to breed in large numbers, make them ideal for high-throughput screening, genetic screening, and significantly shorter experimental times 49 . However, the lack of similarity in retinal vascular structure between zebrafish and humans, difficult handling due to tiny size, and a lack of reagents for molecular studies are factors responsible for the limited use of zebrafish as a screening model for DR 58 .…”

“…These characteristics, combined with their short lifespan, rapid growth, and ability to breed in large numbers, make them ideal for high-throughput screening, genetic screening, and significantly shorter experimental times. 49 However, the lack of similarity in retinal vascular structure between zebrafish and humans, difficult handling due to tiny size, and a lack of reagents for molecular studies are factors responsible for the limited use of zebrafish as a screening model for DR. 58 Regarding neurodegeneration induced by diabetes, there are conflicting results that could be attributed to the different methods used to induce diabetes (immersion-induced hyperglycemia, STZ injection, or genetic models), 66 as well to the regenerative capabilities of the zebrafish retina. 67 In this regard, it should be noted that, unlike mammals, zebrafish are able to regenerate the damaged neuroretina.…”

Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells

“…ROS is induced by PHA and results in cell death. Moreover, the interplay between ROS and autophagy in various diseases has been reported previously [ 42 , 43 ]. To further examine the impact of autophagy on ROS production in breast cancer cells, ROS levels were detected in H 2 DCFDA staining for flow cytometry ( Figure 4 A,C).…”

Insights Into Ferroptosis, a Novel Target for the Therapy of Cancer

“…Autophagy is another form of PCD characterized by the de novo synthesis of organelles enclosed by a double membrane and fused with a lysosome, which leads to their digestion. The main morphology of autophagy is also not present in ferroptosis (15). In all, the morphology of ferroptosis is sensibly different from that of apoptosis, necroptosis, and autophagy.…”