Balance between autophagic pathways preserves retinal homeostasis

Aging Cell

Natalia Rodríguez-Muela²  Hiroshi Koga⁴  Lucía García-Ledo²  Pedro de la Villa³  Enrique J. de la Rosa¹  Ana María Cuervo⁴ 

[1] 3D Lab, Department of Cellular and Molecular Medicine, CIB, CSIC, Madrid, Spain;Department of Cellular and Molecular Biology, CIB, CSIC, Madrid, Spain;Department of Physiology, Universidad de Alcalá, Alcalá de Henares, Spain;Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, USA

关键词: aging;    autophagy;    chaperone‐mediated autophagy;    lipofuscin;    photoreceptor;    retina;   

DOI  :  10.1111/acel.12072

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2013 John Wiley & Sons Ltd and the Anatomical Society