The implication of cell-derived microvesicles in retinal pigment epithelium degeneration
In industrialized countries, degeneration of the macula is the most common cause of irreversible vision loss after 65 years of age and is termed age-related macular degeneration (AMD). This multifactorial disease comprises two types according to the stage of progress: dry AMD (70% of AMD cases) and wet AMD (30% of AMD cases). Dry AMD causes alterations in the retinal pigment epithelium (RPE) whose role in retina homeostasis is critical. These functional and structural alterations are manifested by accumulation of metabolic and cellular waste products in the form of drusen, which appear as lipid-enriched deposits between the RPE and Bruch’s membrane. Oxidative stress is the main contributing factor, which can derive RPE cell blebbing activity and senescence. Despite extensive research; there is still no cure for dry AMD. Our laboratory has long been focusing on the effects of microparticles originating from different cells, such as RPE-derived microparticles (RMPs). Microparticles (MPs) are membrane fragments that are released into environment upon cell activation or apoptosis and are responsible for various biological functions. microRNAs are selectively enriched in microparticles. According to our RNA sequencing profile analysis, let-7f is one of the most abundant microRNA (miRNA) in RMPs, and it may mediate oxidative stress-induced retinal cell dysfunction. The principal objective of this work was to explore the molecular events responsible for RMP-induced RPE cell dysfunction, emphasizing the disruptive signal of let-7f. Our findings strongly indicate that RMPs released by RPE cells under oxidative stress accelerate RPE degeneration and cause subretinal deposits. Given the results regarding let-7f function, this miRNA seems to be the main suspect exerting the detrimental effect of microparticles in RPE cells. In conclusion, verification of the role of RMPs and downstream players such as let-7f in retinal degeneration should inspire the development of therapeutic targets against AMD.
RPE-derived microparticles (RMPs) Oxidative stress RPE cell dysfunction Senescence Phagocytosis MiRNA let-7f Dry-AMD Phagocytose MiARN let-7f