Autophagy Requirements for Eye Lens Differentiation and Transparency

Author:

Brennan Lisa1,Costello M. Joseph2ORCID,Hejtmancik J. Fielding3ORCID,Menko A. Sue45ORCID,Riazuddin S. Amer6,Shiels Alan7,Kantorow Marc1

Affiliation:

1. Department of Biomedical Science, Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33460, USA

2. Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA

3. Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA

4. Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA

5. Department of Ophthalmology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA

6. The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

7. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA

Abstract

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture demonstrate that the low oxygen environment of the lens drives HIF1a-induced autophagy via upregulation of essential mitophagy components to direct the specific elimination of the mitochondria, endoplasmic reticulum, and Golgi apparatus during lens fiber cell differentiation. Pioneering studies on the structural requirements for the elimination of nuclei during lens differentiation reveal the presence of an entirely novel structure associated with degrading lens nuclei termed the nuclear excisosome. Considerable evidence also indicates that autophagy is a requirement for lens homeostasis, differentiation, and transparency, since the mutation of key autophagy proteins results in human cataract formation.

Funder

National Institutes of Health, USA, National Eye Institute, USA

NIH/NEI

Duke Eye Center Core Grant

NEI project ZIA

Publisher

MDPI AG

Subject

General Medicine

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