Abstract
MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age‐related macular degeneration (AMD). Repeated injections with anti‐VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti‐VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR‐34‐5p, miR‐126‐3p, miR‐145‐5p and miR‐205‐5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti‐VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.
Highlights
Age‐related macular degeneration (AMD) is a complex eye disease; it is the leading cause of legal blindness in the elderly in the developed countries
The expression of miR‐34a‐5p may occur in response to oxidative stress, a major factor of AMD pathogenesis.[26] miR‐34a‐5p negatively regulates angiogenesis, which is essential for the development of wet AMD.[27,28]
The up‐regulation of miR‐34a‐5p was reported to be involved in drusen formation in AMD through the down‐regulation of the triggering receptor expressed in myeloid/microglial cells‐2 (TREM2).[29]
Summary
Age‐related macular degeneration (AMD) is a complex eye disease; it is the leading cause of legal blindness in the elderly in the developed countries. Vascular endothelial growth factor A (VEGFA) and its receptor are crucial regulators of choroidal neovascularization (CNV) in wet AMD.[1] The vessels produced in CNV are fragile, and their contents tend to leak into the retina layers, promoting fibrogliosis which results in the formation of a disciform scar and severe loss of vision if not properly treated. Mainly related to the complement system, have been identified as playing either a documented or a putative role in the pathogenesis of AMD, but the role of epigenetic control in AMD is much less clear.[11,12,13] As epigenetic microRNAs (miRNAs) are an important element in the regulation of gene expression, a panel of miRNA species involved in the progression of wet AMD or the conversion of dry AMD into wet AMD should be clarified in order to better understand AMD pathogenesis and to personalize wet AMD therapy. We analysed mortality in the wet AMD patients and control groups without AMD
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