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Sandro Banfi, Marianthi Karali, Irene Guadagnino, Elena Marrocco, Mariateresa Pizzo, Rossella De Cegli, Annamaria Carissimo, Ivan Conte, Enrico Maria Surace; miR-204 overexpression exerts a protective role in inherited retinal diseases. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4927. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Inherited retinal diseases (IRDs) are progressive neurodegenerative conditions of the retina that represent a main cause of genetic blindness in the Western world. Their high genetic heterogeneity hinders the development of effective gene-based therapies. We have recently demonstrated that the microRNA miR-204 is essential for retinal function and plays a pathogenic role in IRD in humans. Therefore, we aimed at assessing the potential therapeutic action of this microRNA in IRDs.
We delivered by subretinal injection an adeno-associated viral vector carrying the miR-204 precursor to the Aipl1knockout and the P347S-RHOtransgenic mouse lines, models of autosomal recessive and dominant forms of IRDs, respectively. The impact on retinal function and degeneration was assessed by electroretinographic and immunohistological analyses.
We detected a notable improvement of the ERG response in the miR-204-injected eyes of P347S-RHOmice. This effect persisted for two months post-injection and was prevalent in conditions reflecting mixed cone-rod responses. We also observed a preservation of cone photoreceptors and a significant decrease in apoptotic photoreceptor cells. Photoreceptors were better preserved also in miR204-injected eyes of Aipl1 knockoutmice. Transcriptome analysis suggested that dampening of microglia activation represents one of the main mechanisms underlying the neuroprotective effect of miR-204.
Our findings indicate that the subretinal delivery of miR-204 attenuates retinal degeneration in IRD mouse models and preserves retinal function, supporting the gene-independent therapeutic potential of this microRNA.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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