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Congxiao Zhang, Kiyoharu j Miyagishima, Lijin Dong, Arvydas Maminishkis, Sheldon S Miller; Targeted deletion of microRNA-204 in mice impairs structure and visual function of RPE and retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6336.
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MicroRNA-204 is one of the two mostly highly expressed microRNAs in human RPE. Previously, it has been shown to determine RPE phenotype by suppressing the apical membrane TGFRβ2. However, it’s in vivo functions in the retina and RPE remain to be fully explored. To dissect the function of miR-204 in the adult eye, we generated and characterized a miR-204 knockout mouse model.
miR-204 KO mice were generated using the BAC- based targeting vector to delete the entire coding sequence of miR-204. The presence of the targeted allele was determined by long range PCR, followed by Southern blotting. Loss of miR-204 expression was verified by miRNA northern blotting and TaqMan® microRNA assay. Ocular structure was evaluated by fundus examination, and histologically using both light and electron microscopy, as well as OCT. Retina and RPE physiology were studied by retinal ERG or direct coupled (DC-ERG), respectively.
Although the miR-204 homozygous eyes displayed normal gross anatomical structure at birth, by 6 weeks of age,morphological defects were observed, as well as deposits in the sub-retinal space that disrupted normal retina and RPE apposition. Fundus images showed hyper-auto fluorescent spots that persisted and increased progressively with age. These structural changes were associated with decreased response amplitudes in the a- and b- waves of the ERG and a decrease in the fast oscillation (FO) of the DC-ERG.
The present experiments suggest an important role for the miR-204 in maintaining the normal structure and function of the RPE and retina in the posterior eye. miR-204 KO mice show impaired retinal/RPE anatomy and light responses and serve as a potential model for the study of RPE barrier function in proliferative eye disease.
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