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Retinal biomarkers and pharmacological targets for Hermansky-Pudlak syndrome 7

Deletion of dystrobrevin binding protein 1 has been linked to Hermansky-Pudlak syndrome type 7 (HPS-7), a rare disease characterized by oculocutaneous albinism and retinal dysfunction. We studied dysbindin-1 null mutant mice (Dys(−/−)) to shed light on retinal neurodevelopment defects in HPS-7. We a...

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Detalles Bibliográficos
Autores principales: Romano, Giovanni Luca, Platania, Chiara Bianca Maria, Leggio, Gian Marco, Torrisi, Sebastiano Alfio, Giunta, Salvatore, Salomone, Salvatore, Purrello, Michele, Ragusa, Marco, Barbagallo, Cristina, Giblin, Frank J., Mastrogiacomo, Rosa, Managò, Francesca, Cammalleri, Maurizio, Papaleo, Francesco, Drago, Filippo, Bucolo, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055265/
https://www.ncbi.nlm.nih.gov/pubmed/32132582
http://dx.doi.org/10.1038/s41598-020-60931-5
Descripción
Sumario:Deletion of dystrobrevin binding protein 1 has been linked to Hermansky-Pudlak syndrome type 7 (HPS-7), a rare disease characterized by oculocutaneous albinism and retinal dysfunction. We studied dysbindin-1 null mutant mice (Dys(−/−)) to shed light on retinal neurodevelopment defects in HPS-7. We analyzed the expression of a focused set of miRNAs in retina of wild type (WT), Dys(+/−) and Dys(−/−) mice. We also investigated the retinal function of these mice through electroretinography (ERG). We found that miR-101-3p, miR-137, miR-186-5p, miR-326, miR-382-5p and miR-876-5p were up-regulated in Dys(−/−)mice retina. Dys(−/−) mice showed significant increased b-wave in ERG, compared to WT mice. Bioinformatic analysis highlighted that dysregulated miRNAs target synaptic plasticity and dopaminergic signaling pathways, affecting retinal functions of Dys(−/−) mice. Overall, the data indicate potential mechanisms in retinal neurodevelopment of Dys(−/−) mice, which may have translational significance in HSP-7 patients, both in terms of diagnostic/prognostic biomarkers and novel pharmacological targets.