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AAV-miR-204 Protects from Retinal Degeneration by Attenuation of Microglia Activation and Photoreceptor Cell Death

Karali, Marianthi ; Guadagnino, Irene ; Marrocco, Elena ; De Cegli, Rossella ; Carissimo, Annamaria ; Pizzo, Mariateresa ; Casarosa, Simona ; Conte, Ivan ; Surace, Enrico Maria ; Banfi, Sandro

Molecular therapy. Nucleic acids, 2020-03, Vol.19, p.144-156 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    AAV-miR-204 Protects from Retinal Degeneration by Attenuation of Microglia Activation and Photoreceptor Cell Death
  • Autor: Karali, Marianthi ; Guadagnino, Irene ; Marrocco, Elena ; De Cegli, Rossella ; Carissimo, Annamaria ; Pizzo, Mariateresa ; Casarosa, Simona ; Conte, Ivan ; Surace, Enrico Maria ; Banfi, Sandro
  • Assuntos: adeno-associated viral vector ; inherited retinal diseases ; microglia ; microRNA ; miR-204 ; photoreceptor degeneration
  • É parte de: Molecular therapy. Nucleic acids, 2020-03, Vol.19, p.144-156
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: Inherited retinal diseases (IRDs) represent a frequent cause of genetic blindness. Their high genetic heterogeneity hinders the application of gene-specific therapies to the vast majority of patients. We recently demonstrated that the microRNA miR-204 is essential for retinal function, although the underlying molecular mechanisms remain poorly understood. Here, we investigated the therapeutic potential of miR-204 in IRDs. We subretinally delivered an adeno-associated viral (AAV) vector carrying the miR-204 precursor to two genetically different IRD mouse models. The administration of AAV-miR-204 preserved retinal function in a mouse model for a dominant form of retinitis pigmentosa (RHO-P347S). This was associated with a reduction of apoptotic photoreceptor cells and with a better preservation of photoreceptor marker expression. Transcriptome analysis showed that miR-204 shifts expression profiles of transgenic retinas toward those of healthy retinas by the downregulation of microglia activation and photoreceptor cell death. Delivery of miR-204 exerted neuroprotective effects also in a mouse model of Leber congenital amaurosis, due to mutations of the Aipl1 gene. Our study highlights the mutation-independent therapeutic potential of AAV-miR204 in slowing down retinal degeneration in IRDs and unveils the previously unreported role of this miRNA in attenuating microglia activation and photoreceptor cell death.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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