Chaperone-mediated autophagy protects against retinal photoreceptor degeneration by modulating proteostasis of glucose metabolism enzymes
show higher resistance to chemically induced photoreceptor degeneration and slower visual function decline. We found a similar protective effect against retinal degeneration upon pharmacological activation of CMA. To start elucidating the mechanisms behind CMA's protective role in the retina, we used comparative proteomics and found elevated levels of enzymes related with glucose metabolism in CMA-deficient retinas that phenocopy those observed in old mice retinas. Overall, our results highlight a cytoprotective role for CMA in retina, in part through proteostatic regulation of enzymes involved in glucose metabolism, and support the feasibility of pharmacologically upregulating CMA against retinal degeneration.
Authors
- Pedro de la Villa (ORCID: https://orcid.org/0000-0001-9856-6616)
- Adrián Martín‐Segura (ORCID: https://orcid.org/0000-0001-9369-0589)
- A. J. Díaz (ORCID: https://orcid.org/0000-0002-1572-3303)
- Raquel Gómez‐Sintes (ORCID: https://orcid.org/0000-0003-2854-6964)
- Concepción Lillo (ORCID: https://orcid.org/0000-0001-5814-9826)
- Ana María Cuervo (ORCID: https://orcid.org/0000-0002-0771-700X)
- Ignacio Ramírez‐Pardo (ORCID: https://orcid.org/0000-0003-4873-7274)
- Patricia Boya (ORCID: https://orcid.org/0000-0003-3045-951X)
- Inmaculada Tasset (ORCID: https://orcid.org/0000-0003-0730-6750)
- Sandra Alonso‐Gil
- Evripidis Gavathiotis (ORCID: https://orcid.org/0000-0001-6319-8331)
- Kristen Lindenau (ORCID: https://orcid.org/0000-0001-6145-5322)
- Simone Sidoli (ORCID: https://orcid.org/0000-0001-9073-6641)
Institutions
- Albert Einstein College of Medicine (US)
- University of Fribourg (CH)
- Universidad de Alcalá (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Instituto de Estudios de Ciencias de la Salud de Castilla y León (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Centro de Investigaciones Biológicas Margarita Salas (ES)
- Cordoba University (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-05-11
- DOI
- https://doi.org/10.1073/pnas.2527503123
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministerio de Ciencia, Innovación y Universidades
- Ministerio de Ciencia e Innovación
- National Institute on Aging
- Freedom Together Foundation