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Proteases in Lens and Cataract

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Studies on the Cornea and Lens

Abstract

The eye lens is a transparent tissue with a unique cellular architecture and pattern of development. Several proteases play pivotal roles during lens morphogenesis and thereafter to maintain the lens transparency. However, with aging, the activity of a number of lens proteases changes, resulting in the degradation of lens proteins and the accumulation of protein fragments. Recent studies suggest that some of the protein fragments that accumulate in the lens with age might be involved in aggregation of lens proteins and development of opacity, also known as cataract. In vitro and in vivo experiments show that lens opacity from α-crystallin aggregation bears the hallmarks of increased proteolysis and decreased α-crystallin chaperone activity. A number of lens proteases are now implicated in the degradation of cytoskeletal proteins, the truncation of lens crystallins, and the generation of peptides that have a role in aggregation and precipitation of lens proteins culminating in cataract. While a perfect animal model to understand the mechanisms of cataractogenesis has yet to be developed, the experimental models now available, such as transgenic mice that overexpress acylpeptide hydrolase, allow study of the lens proteases and the potential therapeutic targets.

This review chapter is dedicated to the memory of Dr. Beryl J. Ortwerth

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Abbreviations

APH:

Acylpeptide hydrolase

LC-MS:

Liquid chromatography mass spectrometry

LMW:

Low molecular weight

WIS:

Water-insoluble

WS:

Water-soluble

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Acknowledgments

We thank Brian Mooney, Ph.D. from the University of Missouri Proteomic Core for the help and discussions in the mass spectrometric analysis of the peptides and Sharon Morey for help in the preparation of the manuscript. Work in author’s laboratory is supported in part by National Institutes of Health grants EY023219 and EY019878.

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Authors and Affiliations

  1. Department of Ophthalmology, University of Missouri—Columbia School of Medicine, Columbia, MO, USA

    Puttur Santhoshkumar

  2. Departments of Ophthalmology and Biochemistry, University of Missouri—Columbia School of Medicine, Columbia, MO, USA

    Rama Kannan & K. Krishna Sharma

  3. Department of Ophthalmology, University of Missouri School of Medicine, Columbia, MO, 65212, USA

    K. Krishna Sharma

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  1. Puttur Santhoshkumar
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  2. Rama Kannan
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  3. K. Krishna Sharma
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Corresponding author

Correspondence to K. Krishna Sharma .

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Editors and Affiliations

  1. Innovative Vision Products Inc., Moscow, Russia, Innovative Vision Products, Inc.,, County of New Castle, Delaware, USA

    Mark A. Babizhayev

  2. Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, College of Medicine, University of Nebraska Medical Center; Key Laboratory of Protein Chemistry and Developmental Biology of Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China, Omaha, Nebraska, USA

    David Wan-Cheng Li

  3. Department of Pharmaceutical Sciences and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Anne Kasus-Jacobi

  4. Department of Ophthalmology, University of Pristina, Faculty of Medicine, Kosovska Mitrovica, Serbia

    Lepša Žorić

  5. Ophthalmology, Miguel Hernandez University, Alicante, Spain

    Jorge L. Alió

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Santhoshkumar, P., Kannan, R., Sharma, K.K. (2015). Proteases in Lens and Cataract. In: Babizhayev, M., Li, DC., Kasus-Jacobi, A., Žorić, L., Alió, J. (eds) Studies on the Cornea and Lens. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1935-2_13

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