Abstract
Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3′UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.
Highlights
Age-related macular degeneration (AMD) is one of the principle causes of central vision decline and irreversible blindness in the elderly over 50 years old [1, 2]
To investigate the influences of blue light-emitting diode (LED) emissions on retinal morphology, hematoxylin and eosin (H&E) staining was conducted at the time points of 0 h, 3 d, 7 d, 14 d, and 28 d after blue LED stimuli
It is noticeable that rapamycin enhanced the cell viability in the NC group but with a lesser extent in the miR-27a and siFOXO1 group. These results indicated that the inhibition of autophagy by miR-27a-FOXO1 axis caused a cell viability decrease when they are exposed on H2O2, while the promotion of autophagy by rapamycin partially rescued this H2O2-induced cell death if the miR-27a-FOXO1 axis is not extremely aberrant activated
Summary
Age-related macular degeneration (AMD) is one of the principle causes of central vision decline and irreversible blindness in the elderly over 50 years old [1, 2]. It has been estimated that the number of patients diagnosed with AMD will reach 288 million by 2040 [3]. The most severe challenge to us is the lack of effective diagnostic strategies and interventions for early-stage AMD. Most patients are diagnosed at advanced stages and develop geographic atrophy (GA) or choroidal neovascularization (CNV) in the macula, leading to severe retinal pigment epithelial (RPE) cell and photoreceptor loss and irreversible blindness [4]. RPE plays a role as protector and scavenger to the retina. The main function of RPE is to maintain the blood-retinal barrier and phagocyte photoreceptor outer segment disks. In early AMD, RPE dysfunction is thought to be the primary change, after which progressive photoreceptor loss occurs. The health of RPE is of great importance to retinal function. Since the retina is a high oxygen demanding tissue, continu-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
