July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
miR-204 overexpression exerts a protective role in inherited retinal diseases
Author Affiliations & Notes
  • Sandro Banfi
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
    Precision Medicine, University of Campania "Luigi Vanvitelli", Italy
  • Marianthi Karali
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
    Precision Medicine, University of Campania "Luigi Vanvitelli", Italy
  • Irene Guadagnino
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
  • Elena Marrocco
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
  • Mariateresa Pizzo
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
  • Rossella De Cegli
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
  • Annamaria Carissimo
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
  • Ivan Conte
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
  • Enrico Maria Surace
    Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), Italy
    Translational Medicine, Federico II University, Naples, Italy
  • Footnotes
    Commercial Relationships   Sandro Banfi, None; Marianthi Karali, None; Irene Guadagnino, None; Elena Marrocco, None; Mariateresa Pizzo, None; Rossella De Cegli, None; Annamaria Carissimo, None; Ivan Conte, None; Enrico Maria Surace, None
  • Footnotes
    Support  Foundation Fighting Blindness grant TA-NMT-0616-0701-TIGM and Italian Telethon Foundation grant TGM16YGM02
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4927. doi:https://doi.org/
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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