Description
Defective proteostasis is one of the hallmarks of aging cells and tissues. Of the different components of the proteostasis network, we are interested in autophagy and its changes with age in retina. We have previously shown that, out of the different autophagic pathways that co-exist in all mammalian cells, macroautophagy is the first that declines with age in the retina. A crosstalk between macroautophagy and chaperone mediated autophagy (CMA) has been described whereby, in aged mice retinas, the decrease in macroautophagy correlates with increased CMA. Our working hypothesis is that aged and degenerated retinal cells increase CMA to compensate for macroautophagy loss, in an attempt to maintain cell viability. To test our hypothesis, we use histological and biochemical analysis, but also functional read outs as electroretinogram (ERG) or optic coherence tomography (OCT) and visual behavioural tests. If proven correct, increasing CMA could be a potential treatment to delay consequences of aging in the retina and to ameliorate degeneration in age-related retinal pathologies.
Selected Publications
Targeting retinoic acid receptor alpha-corepressor interaction activates chaperone-mediated autophagy and protects against retinal degeneration. Gomez-Sintes R, Xin Q, Jimenez-Loygorri JI, McCabe M, Diaz A, Garner TP, Cotto-Rios XM, Wu Y, Dong S, Reynolds CA, Patel B, de la Villa P, Macian F, Boya P, Gavathiotis E, Cuervo AM. Nat Commun. 2022 Jul 21;13(1):4220.
HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice. Samardzija M, Corna A, Gomez-Sintes R, Jarboui MA, Armento A, Roger JE, Petridou E, Haq W, Paquet-Durand F, Zrenner E, de la Villa P, Zeck G, Grimm C, Boya P, Ueffing M, Trifunović D. Cell Death Differ. 2020 Nov 6.
Standard Assays for the Study of Autophagy in the Ex Vivo Retina. Gómez-Sintes R, Villarejo-Zori B, Serrano-Puebla A, Esteban-Martínez L, Sierra-Filardi E, Ramírez-Pardo I, Rodríguez-Muela N, Boya P. Cells. 2017 Oct 22;6(4).
Glycogen synthase kinase-3β regulates fractalkine production by altering its trafficking from Golgi to plasma membrane: implications for Alzheimer's disease. Fuster-Matanzo A, Jurado-Arjona J, Benvegnù S, García E, Martín-Maestro P, Gómez-Sintes R, Hernández F, Ávila J. Cell Mol Life Sci. 2017 Mar;74(6):1153-1163.
Lysosomal membrane permeabilization and cell death. Wang F, Gómez-Sintes R, Boya P. Traffic. 2018 Dec;19(12):918-931.
Lysosomal cell death mechanisms in aging. Gómez-Sintes R, Ledesma MD, Boya P. Ageing Res Rev. 2016 Dec;32:150-168.
Autophagy in the eye: Development, degeneration, and aging. Boya P, Esteban-Martínez L, Serrano-Puebla A, Gómez-Sintes R, Villarejo-Zori B. Prog Retin Eye Res. 2016 Nov;55:206-245.
Pathogenic lysosomal depletion in Parkinson's disease. Dehay B, Bové J, Rodríguez-Muela N, Perier C, Recasens A, Boya P*, Vila M*. J Neurosci. 2010;30:12535-44.
Group