Abstract
As increases in hepatocyte growth factor/scatter factor (HGF/SF) induce retinal pigment epithelial (RPE) migration and proliferation into the vitreous cavity and contribute to proliferative vitreoretinopathy (PVR) development, we determined if changes in miR-182 expression affect such behavioral changes. We found that miR-182 expression was less in PVR clinical samples than in primary RPE cells whereas c-Met was upregulated. Ectopic miR-182 inhibited RPE cell proliferation, cell cycle, and migration. Bioinformatic analysis identified c-Met as a miR-182 target, which was confirmed with the luciferase reporter assay. Transfection of miR-182 into RPE cells induced c-Met downregulation, which led to reduced cell proliferation and migration through declines in p-Akt formation. MiR-182 downregulation along with c-Met upregulation in PVR tissues suggest that these two opposing effects play important roles in PVR development. As ectopic miR-182 expression suppressed RPE cell proliferation and migration, strategies to selectively upregulate miR-182 expression in a clinical setting may provide a novel option to treat this disease.
Highlights
Proliferative vitreoretinopathy (PVR) is a sight compromising pathological response to either retinal reattachment surgery or ocular trauma
In six PVR clinical specimens, miR-182 levels were significantly downregulated compared to those in retinal pigment epithelial (RPE) cells used as normal controls (Fig 1)
The marked miR-182 decrease in PVR clinical samples prompted us to determine in PVR whether or not such a decline may contribute to increases in RPE proliferation occurring in this disease process
Summary
Proliferative vitreoretinopathy (PVR) is a sight compromising pathological response to either retinal reattachment surgery or ocular trauma. This condition arises from retinal detachment surgery in 5–10% of the cases leading to scarring and inflammation during wound healing [1,2,3,4,5]. These side effects are accompanied by formation of sight compromising epiretinal membranes containing a mixture of different retinal derived cell types. They include retinal pigment epithelial (RPE) cells, glial and Muller cells as well as fibroblasts and activated immune cells that are induced to translocate into the vitreous chamber and elaborate these
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