Mitochondrial quality control in AMD: does mitophagy play a pivotal role?

Abstract

Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle's homeostasis. The abundance of ROS, DNA damage, and the excessive energy consumption in the ageing retina all contribute to the degeneration of RPE cells and their mitochondria. We discuss the role of mitophagy in the cell and argue that its impairment may play a role in AMD pathogenesis. Thus, mitophagy as a potential therapeutic target in AMD and other degenerative diseases is as well explored.

Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells

“…These data suggest that RPE cells lacking FH are unsuccessfully trying to respond to an oxidative stress situation. Another mechanism of mitochondrial quality control is mitophagy, a mitochondria specific autophagy [29]. We found a significant alteration in the expression levels of genes regulating mitophagy (Fig 6A), like PTEN induced putative kinase 1 (PINK1) and E3 Ubiquitin-Protein Ligase Parkin (PARKIN) and mitochondria dynamics (Fig 6B), like Dynamin-Related Protein 1 (DRP1) and OPA1 Mitochondrial Dynamin Like GTPase (OPA1) when FH was missing (Fig 6B).…”

“…Cells have developed alternative mechanisms to overcome mitochondrial dysfunction which are activated in case of damage. Mitophagy is a specific type of autophagy directed in eliminating unnecessary, damaged or malfunctioning mitochondria [29]. Mitophagy is classically mediated by the PINK-PARKIN axes [56], and both genes were upregulated in RPE cells when FH levels were reduced.…”

Peroxisome turnover and diurnal modulation of antioxidant activity in retinal pigment epithelia utilizes microtubule-associated protein 1 light chain 3B

“…Reduced autophagic flux, accompanied by accumulation of autophagosomes and lysosomes, in RPE derived from AMD patients was proposed to contribute to poor mitophagy and mitochondrial dysfunction (29). The role for autophagic degradation in mitochondrial quality control in AMD has been the subject of more intense focus (32). Mitochondria and peroxisomes intimately cooperate in metabolic pathways and regulation of ROS.…”

Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update

“…OS occurs in the above conditions and plays a vital role in the pathogenesis of AMD. AMD is associated with the progressive degeneration and death of RPEs, followed by adverse effects on rods and cones [139]. The ROS level was shown to be significantly higher in the RPEs of AMD patients than in those of a control group [140,141].…”