title: Balance between autophagic pathways preserves retinal homeostasis.
abstract: Aging contributes to the appearance of several retinopathies and is the largest risk factor for aged-related macular degeneration, major cause of blindness in the elderly population. Accumulation of undegraded material as lipofuscin represents a hallmark in many pathologies of the aged eye. Autophagy is a highly conserved intracellular degradative pathway that plays a critical role in the removal of damaged cell components to maintain the cellular homeostasis. A decrease in autophagic activity with age observed in many tissues has been proposed to contribute to the aggravation of age-related diseases. However, the participation of different autophagic pathways to the retina physiopathology remains unknown. Here, we describe a marked reduction in macroautophagic activity in the retina with age, which coincides with an increase in chaperone-mediated autophagy (CMA). This increase in CMA is also observed during retinal neurodegeneration in the Atg5(flox/flox) ; nestin-Cre mice, a mouse model with downregulation of macroautophagy in neuronal precursors. In contrast to other cell types, this autophagic cross talk in retinal cells is not bi-directional and CMA inhibition renders cone photoreceptor very sensitive to stress. Temporal and cell-type-specific differences in the balance between autophagic pathways may be responsible for the specific pattern of visual loss that occurs with aging. Our results show for the first time a cross talk of different lysosomal proteolytic systems in the retina during normal aging and may help the development of new therapeutic intervention for age-dependent retinal diseases.
authors.affiliation: Department of Cellular and Molecular Biology, CIB, CSIC, Ramiro de Maeztu 9, E-28040, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rodríguez-Muela
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.forename: Lucía
authors.initials: L
authors.lastname: García-Ledo
authors.forename: Pedro
authors.initials: P
authors.lastname: de la Villa
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: de la Rosa
authors.forename: Ana María
authors.initials: AM
authors.lastname: Cuervo
authors.forename: Patricia
authors.initials: P
authors.lastname: Boya
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002460:Cell Line; D016922:Cellular Senescence; D005260:Female; D006706:Homeostasis; D008268:Macular Degeneration / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012160:Retina / Q000502:physiology* / Q000503:physiopathology