Balance between autophagic pathways preserves retinal homeostasis

Natalia Rodríguez-Muela, Hiroshi Koga, Lucía García-Ledo, Pedro de la Villa, Enrique J. de la Rosa, Ana María Cuervo, Patricia Boya

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


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 Atg5flox/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.

Original languageEnglish (US)
Pages (from-to)478-488
Number of pages11
JournalAging cell
Issue number3
StatePublished - Jun 2013


  • Aging
  • Autophagy
  • Chaperone-mediated autophagy
  • Lipofuscin
  • Photoreceptor
  • Retina

ASJC Scopus subject areas

  • Aging
  • Cell Biology


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