Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease.
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Proceedings of the National Academy of Sciences of the United States of America
2026
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| author | Brillante, Simona Volpe, Mariagrazia Diana, Anna Negueruela, Santiago Molinari, Marta Saurino, Rosa Cipollaro, Eva Polishchuk, Elena Tenderini, Erika Damiano, Carla Tornabene, Patrizia Polishchuk, Roman Parenti, Giancarlo Tarallo, Antonietta Banfi, Sandro Trapani, Ivana Carrella, Sabrina Indrieri, Alessia |
| author_facet | Brillante, Simona Volpe, Mariagrazia Diana, Anna Negueruela, Santiago Molinari, Marta Saurino, Rosa Cipollaro, Eva Polishchuk, Elena Tenderini, Erika Damiano, Carla Tornabene, Patrizia Polishchuk, Roman Parenti, Giancarlo Tarallo, Antonietta Banfi, Sandro Trapani, Ivana Carrella, Sabrina Indrieri, Alessia Brillante, Simona Volpe, Mariagrazia Diana, Anna Negueruela, Santiago Molinari, Marta Saurino, Rosa Cipollaro, Eva Polishchuk, Elena Tenderini, Erika Damiano, Carla Tornabene, Patrizia Polishchuk, Roman Parenti, Giancarlo Tarallo, Antonietta Banfi, Sandro Trapani, Ivana Carrella, Sabrina Indrieri, Alessia |
| collection | PubMed - marine biology |
| contents | Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease. Brillante, Simona Volpe, Mariagrazia Diana, Anna Negueruela, Santiago Molinari, Marta Saurino, Rosa Cipollaro, Eva Polishchuk, Elena Tenderini, Erika Damiano, Carla Tornabene, Patrizia Polishchuk, Roman Parenti, Giancarlo Tarallo, Antonietta Banfi, Sandro Trapani, Ivana Carrella, Sabrina Indrieri, Alessia Animals Stargardt Disease MicroRNAs Mitochondria Mice Humans Retinal Pigment Epithelium ATP-Binding Cassette Transporters Macular Degeneration GTP Phosphohydrolases Mice, Knockout Disease Models, Animal Organoids Photoreceptor Cells, Vertebrate Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in , which result in the progressive degeneration of the retinal pigment epithelium (RPE), ultimately leading to photoreceptor loss. Despite extensive efforts, STGD1 currently lacks effective treatments. Here, we first identified mitochondrial defects in the photoreceptors of mice and STGD1 patient-derived retinal organoids. Specifically, we found reduced mitochondrial content, defective cristae morphology, and downregulation of OPA1, a critical regulator of mitochondrial integrity, demonstrating that photoreceptor defects in STGD1 also have a cell-autonomous origin, besides the RPE dysfunction. Importantly, we also demonstrated that correcting this pathological phenotype through the modulation of microRNAs 181a and b (miR-181a/b), key regulators of mitochondrial function, ameliorates the STGD1 phenotype. Indeed, genetic inactivation and adeno-associated viral vector-mediated silencing of miR-181a/b in STGD1 models restored OPA1 levels, improved mitochondrial phenotype, and reduced lipofuscin accumulation in the RPE. Our study demonstrates that mitochondrial dysfunction in photoreceptors is an important contributor to STGD1 pathology, opening promising therapeutic avenues for this disorder. |
| format | Artículo científico |
| id | pubmed_41984830 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Proceedings of the National Academy of Sciences of the United States of America |
| record_format | pubmed |
| spellingShingle | Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease. Brillante, Simona Volpe, Mariagrazia Diana, Anna Negueruela, Santiago Molinari, Marta Saurino, Rosa Cipollaro, Eva Polishchuk, Elena Tenderini, Erika Damiano, Carla Tornabene, Patrizia Polishchuk, Roman Parenti, Giancarlo Tarallo, Antonietta Banfi, Sandro Trapani, Ivana Carrella, Sabrina Indrieri, Alessia Animals Stargardt Disease MicroRNAs Mitochondria Mice Humans Retinal Pigment Epithelium ATP-Binding Cassette Transporters Macular Degeneration GTP Phosphohydrolases Mice, Knockout Disease Models, Animal Organoids Photoreceptor Cells, Vertebrate Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease. Brillante, Simona Volpe, Mariagrazia Diana, Anna Negueruela, Santiago Molinari, Marta Saurino, Rosa Cipollaro, Eva Polishchuk, Elena Tenderini, Erika Damiano, Carla Tornabene, Patrizia Polishchuk, Roman Parenti, Giancarlo Tarallo, Antonietta Banfi, Sandro Trapani, Ivana Carrella, Sabrina Indrieri, Alessia Animals Stargardt Disease MicroRNAs Mitochondria Mice Humans Retinal Pigment Epithelium ATP-Binding Cassette Transporters Macular Degeneration GTP Phosphohydrolases Mice, Knockout Disease Models, Animal Organoids Photoreceptor Cells, Vertebrate Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in , which result in the progressive degeneration of the retinal pigment epithelium (RPE), ultimately leading to photoreceptor loss. Despite extensive efforts, STGD1 currently lacks effective treatments. Here, we first identified mitochondrial defects in the photoreceptors of mice and STGD1 patient-derived retinal organoids. Specifically, we found reduced mitochondrial content, defective cristae morphology, and downregulation of OPA1, a critical regulator of mitochondrial integrity, demonstrating that photoreceptor defects in STGD1 also have a cell-autonomous origin, besides the RPE dysfunction. Importantly, we also demonstrated that correcting this pathological phenotype through the modulation of microRNAs 181a and b (miR-181a/b), key regulators of mitochondrial function, ameliorates the STGD1 phenotype. Indeed, genetic inactivation and adeno-associated viral vector-mediated silencing of miR-181a/b in STGD1 models restored OPA1 levels, improved mitochondrial phenotype, and reduced lipofuscin accumulation in the RPE. Our study demonstrates that mitochondrial dysfunction in photoreceptors is an important contributor to STGD1 pathology, opening promising therapeutic avenues for this disorder. |
| title | Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease. |
| topic | Animals Stargardt Disease MicroRNAs Mitochondria Mice Humans Retinal Pigment Epithelium ATP-Binding Cassette Transporters Macular Degeneration GTP Phosphohydrolases Mice, Knockout Disease Models, Animal Organoids Photoreceptor Cells, Vertebrate |
| url | https://pubmed.ncbi.nlm.nih.gov/41984830/ |