Ambra1 haploinsufficiency in cd1 mice results in metabolic alterations and exacerbates age-associated retinal degeneration
| العنوان: | Ambra1 haploinsufficiency in cd1 mice results in metabolic alterations and exacerbates age-associated retinal degeneration |
|---|---|
| المؤلفون: | Ignacio Ramírez-Pardo, Beatriz Villarejo-Zori, Juan Ignacio Jiménez-Loygorri, Elena Sierra-Filardi, Sandra Alonso-Gil, Guillermo Mariño, Pedro de la Villa, Patrick S Fitze, José Manuel Fuentes, Ramón García-Escudero, Deborah A. Ferrington, Raquel Gomez-Sintes, Patricia Boya |
| المساهمون: | European Commission, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Ramírez-Pardo, Ignacio [0000-0003-4873-7274], Jiménez-Loygorri, Juan Ignacio [0000-0002-3065-9952], Sierra-Filardi, Elena [0000-0003-4439-2037], Mariño, Guillermo [0000-0003-1960-1677], de la Villa, P. [0000-0001-9856-6616], Fitze, Patrick S. [0000-0002-6298-2471], Fuentes, José M. [0000-0001-6910-2089], García-Escudero, Ramón [0000-0001-5640-6542], Gómez-Sintes, Raquel [0000-0003-2854-6964], Boya, Patricia [0000-0003-3045-951X], Ramírez-Pardo, Ignacio, Jiménez-Loygorri, Juan Ignacio, Sierra-Filardi, Elena, Mariño, Guillermo, de la Villa, P., Fitze, Patrick S., Fuentes, José M., García-Escudero, Ramón, Gómez-Sintes, Raquel, Boya, Patricia |
| المصدر: | Scopus Digital.CSIC. Repositorio Institucional del CSIC instname |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Aging, Retinal pigment, Autophagy, Metabolic alterations, Cell Biology, AMBRA1, Neurodegeneration, Molecular Biology, Retina, Epithelium |
| الوصف: | 22 p.-9 fig. Macroautophagy/autophagy is a key process in the maintenance of cellular homeostasis. The age-dependent decline in retinal autophagy has been associated with photoreceptor degeneration. Retinal dysfunction can also result from damage to the retinal pigment epithelium (RPE), as the RPE-retina constitutes an important metabolic ecosystem that must be finely tuned to preserve visual function. While studies of mice lacking essential autophagy genes have revealed a predisposition to retinal degeneration, the consequences of a moderate reduction in autophagy, similar to that which occurs during physiological aging, remain unclear. Here, we described a retinal phenotype consistent with accelerated aging in mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene. These mice showed protein aggregation in the retina and RPE, metabolic underperformance, and premature vision loss. Moreover, Ambra1+/gt mice were more prone to retinal degeneration after RPE stress. These findings indicate that autophagy provides crucial support to RPE-retinal metabolism and protects the retina against stress and physiological aging. This work was supported by the H2020 Excellent Science [No. 765912]; Instituto de Salud Carlos III,CiberNed [CB06/05/0041]; Spanish Ministry of Science and Innovation [RTI2018-098990-J-I00]; Spanish Ministry of Science and Innovation [PGC2018-098557-B-I00]. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c5d39e5a0ae225eaae1cc82a7b1f02c2 http://hdl.handle.net/10651/66645 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c5d39e5a0ae225eaae1cc82a7b1f02c2 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |