Autophagy Dysfunction, Cellular Senescence, and Abnormal Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic Potential.

Shoubi Wang,Jiahui Liu,Xuan Sang,Yaru Su,Xiaoran Wang,Ying Liu,Yaqi Cheng,Lin Jin,Weijie Ouyang,Liu Yang,Zhichong Wang,Chaoyang Li

doi:10.1155/2019/3632169

Abstract

Age-related macular degeneration (AMD) is a blinding disease caused by multiple factors and is the primary cause of vision loss in the elderly. The morbidity of AMD increases every year. Currently, there is no effective treatment option for AMD. Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) is currently the most widely used therapy, but it only aims at neovascularization, which is an intermediate pathological phenomenon of wet AMD, not at the etiological treatment. Anti-VEGF therapy can only temporarily delay the degeneration process of wet AMD, and AMD is easy to relapse after drug withdrawal. Therefore, it is urgent to deepen our understanding of the pathophysiological processes underlying AMD and to identify integrated or new strategies for AMD prevention and treatment. Recent studies have found that autophagy dysfunction in retinal pigment epithelial (RPE) cells, cellular senescence, and abnormal immune-inflammatory responses play key roles in the pathogenesis of AMD. For many age-related diseases, the main focus is currently the clearing of senescent cells (SNCs) as an antiaging treatment, thereby delaying diseases. However, in AMD, there is no relevant antiaging application. This review will discuss the pathogenesis of AMD and how interactions among RPE autophagy dysfunction, cellular senescence, and abnormal immune-inflammatory responses are involved in AMD, and it will summarize the three antiaging strategies that have been developed, with the aim of providing important information for the integrated prevention and treatment of AMD and laying the ground work for the application of antiaging strategies in AMD treatment.

Highlights

Age-related macular degeneration (AMD) is the leading cause of visual impairment among the elderly in western countries
It has been previously demonstrated that oxidative stress [3], aging [4], DNA damage [5], and ultraviolet radiation [6] can lead to AMD by influencing the autophagy function of retinal pigment epithelial (RPE) cells, cellular senescence, and the immune-inflammatory response, which are closely
These findings suggest that autophagy dysfunction in RPE cells, cellular senescence, and abnormal immuneinflammatory responses are involved in AMD pathogenesis and promote its progress

Summary

Introduction

AMD is the leading cause of visual impairment among the elderly in western countries. It has been previously demonstrated that oxidative stress [3], aging [4], DNA damage [5], and ultraviolet radiation [6] can lead to AMD by influencing the autophagy function of RPE cells, cellular senescence, and the immune-inflammatory response, which are closely. The abovementioned factors interact with each other, causing lipofuscin deposition, drusen formation, RPE injury, or atrophy, which can lead to photoreceptor cell damage, choroid degeneration, and loss of vision. These findings suggest that autophagy dysfunction in RPE cells, cellular senescence, and abnormal immuneinflammatory responses are involved in AMD pathogenesis and promote its progress. We review the pathophysiological processes and interactions that are involved in AMD, with the aim of providing important information for the molecular, biological, and clinical research of AMD in the future

Autophagy Dysfunction Leads to “Clearance System” Abnormalities

Abnormal Immune-Inflammatory Responses

Findings

Conclusion