In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration
Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders characterized by progressive photoreceptor degeneration and irreversible vision loss. MicroRNAs (miRNAs), a class of endogenous non-coding RNAs with post-transcriptional regulatory properties, are known to play...
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003214 |
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| author | Georgios Petrogiannakis Irene Guadagnino Santiago Negueruela Martina Di Guida Elena Marrocco Mariateresa Pizzo Annalaura Torella Mariateresa Zanobio Marianthi Karali Diego Luis Medina Sabrina Carrella Sandro Banfi |
| author_facet | Georgios Petrogiannakis Irene Guadagnino Santiago Negueruela Martina Di Guida Elena Marrocco Mariateresa Pizzo Annalaura Torella Mariateresa Zanobio Marianthi Karali Diego Luis Medina Sabrina Carrella Sandro Banfi |
| author_sort | Georgios Petrogiannakis |
| collection | DOAJ |
| description | Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders characterized by progressive photoreceptor degeneration and irreversible vision loss. MicroRNAs (miRNAs), a class of endogenous non-coding RNAs with post-transcriptional regulatory properties, are known to play a major role in retinal function, both in physiological and pathological conditions. Given their ability to simultaneously modulate multiple molecular pathways, miRNAs represent promising therapeutic tools for disorders with high genetic heterogeneity, such as IRDs. In the present study, we performed high-content imaging (HCI) screening to assess the impact of miRNA overexpression on a photoreceptor cell line undergoing light-induced degeneration. More than 1,200 miRNAs were assayed for putative protective effects in light-stressed 661W photoreceptor-like cells, and the top-performing miRNAs were further validated in independent in vitro assays. miR-429 showed the strongest cell-protective effect in vitro. Adeno-associated viral vector-mediated subretinal delivery of miR-429 in the RhoP23H/+ IRD mouse model preserved electrophysiological responses and was associated with reduced inflammatory processes in the retina. We demonstrate that the HCI in vitro assay we devised is a reliable screening method to select candidate molecules for mutation-independent therapeutic approaches for retinal disorders. Moreover, our data indicate that miR-429 represents a potential therapeutic target against photoreceptor degeneration. |
| format | Article |
| id | doaj-art-ee74cd04ccab45f288b683da357aced3 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-ee74cd04ccab45f288b683da357aced32025-01-12T05:24:52ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102434In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degenerationGeorgios Petrogiannakis0Irene Guadagnino1Santiago Negueruela2Martina Di Guida3Elena Marrocco4Mariateresa Pizzo5Annalaura Torella6Mariateresa Zanobio7Marianthi Karali8Diego Luis Medina9Sabrina Carrella10Sandro Banfi11Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy; Department of Environmental, Biological and Pharmaceutical Science and Technology, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100 Caserta, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy; Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 7, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 7, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 7, 80138 Naples, Italy; Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, University of Campania “Luigi Vanvitelli”, Via Pansini 5, 80131 Naples, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy; Department of Medical and Translational Science, Federico II University, 80131 Naples, ItalyBiology and Evolution of Marine Organisms Department, Stazione Zoologica Anton Dohrn, Villa Comunale, 80133 Naples, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy; Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 7, 80138 Naples, Italy; Corresponding author: Sandro Banfi, Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy.Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders characterized by progressive photoreceptor degeneration and irreversible vision loss. MicroRNAs (miRNAs), a class of endogenous non-coding RNAs with post-transcriptional regulatory properties, are known to play a major role in retinal function, both in physiological and pathological conditions. Given their ability to simultaneously modulate multiple molecular pathways, miRNAs represent promising therapeutic tools for disorders with high genetic heterogeneity, such as IRDs. In the present study, we performed high-content imaging (HCI) screening to assess the impact of miRNA overexpression on a photoreceptor cell line undergoing light-induced degeneration. More than 1,200 miRNAs were assayed for putative protective effects in light-stressed 661W photoreceptor-like cells, and the top-performing miRNAs were further validated in independent in vitro assays. miR-429 showed the strongest cell-protective effect in vitro. Adeno-associated viral vector-mediated subretinal delivery of miR-429 in the RhoP23H/+ IRD mouse model preserved electrophysiological responses and was associated with reduced inflammatory processes in the retina. We demonstrate that the HCI in vitro assay we devised is a reliable screening method to select candidate molecules for mutation-independent therapeutic approaches for retinal disorders. Moreover, our data indicate that miR-429 represents a potential therapeutic target against photoreceptor degeneration.http://www.sciencedirect.com/science/article/pii/S2162253124003214MT: Non-coding RNAsinherited retinal diseasesphotoreceptor degenerationmicroRNAhigh-content screeninglight-induced degeneration |
| spellingShingle | Georgios Petrogiannakis Irene Guadagnino Santiago Negueruela Martina Di Guida Elena Marrocco Mariateresa Pizzo Annalaura Torella Mariateresa Zanobio Marianthi Karali Diego Luis Medina Sabrina Carrella Sandro Banfi In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration Molecular Therapy: Nucleic Acids MT: Non-coding RNAs inherited retinal diseases photoreceptor degeneration microRNA high-content screening light-induced degeneration |
| title | In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration |
| title_full | In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration |
| title_fullStr | In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration |
| title_full_unstemmed | In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration |
| title_short | In vitro high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration |
| title_sort | in vitro high content screening reveals mir 429 as a protective molecule in photoreceptor degeneration |
| topic | MT: Non-coding RNAs inherited retinal diseases photoreceptor degeneration microRNA high-content screening light-induced degeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003214 |
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