A Functional Study Of MiR-204 In Age-related Macular Degeneration

Purpose:Dysfunction of the retinal pigmented epithelium（RPE）results in the degeneration of photoreceptors and vision loss and is correlated with common blinding disorders in humans.MicroRNAs were found to be indispensable for maintaining RPE fate and survival.The purpose of this study was to determine the potential role of miR-204 in the pathogenesis of retinal degenerative disease.Methods:Immunofluorescence of retinal sections,western blot and qRT-PCR were used to analyze the protein and mRNA expression.RPE morphology was examined by RPE-flat mounts and transmission electron microscope（TEM）.Retinal degeneration was monitored by eye fundus and electroretinography（ERG）and spectral domain optical coherence tomography（SD-OCT）.Results:Immunofluorescence,western blot and qRT-PCR results showed loss of a series of RPE-characteristic markers in miR-204^-/-mice when compared with control mice.Eye fundus showed white deposits in miR-204^-/-mice.Dark-adapted ERG analysis showed that miR-204^-/-mice displayed a significantly reduced rod responses（a-wave and b-wave）when compared with control mice.SD-OCT analysis of miR204^-/-mice showed that the photoreceptor IS/OS junction line was absent compared to age-matched control mice.TEM examination revealed that miR204^-/-basal infoldings were disorganized.Conclusion:These results suggest a critical role of miR-204 in maintaining epithelial barrier function and the development of the adjacent neuroretina and miR-204^-/-mice may serve as a new animal model to understand the pathogenesis of retinal degenerative disease.