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Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

Quinlan, Roy A.; Clark, John I.

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Authors

John I. Clark



Abstract

In the human eye, a transparent cornea and lens combine to form the “refracton” to focus images on the retina. This requires the refracton to have a high refractive index “n,” mediated largely by extracellular collagen fibrils in the corneal stroma and the highly concentrated crystallin proteins in the cytoplasm of the lens fiber cells. Transparency is a result of short-range order in the spatial arrangement of corneal collagen fibrils and lens crystallins, generated in part by post-translational modifications (PTMs). However, while corneal collagen is remodeled continuously and replaced, lens crystallins are very long-lived and are not replaced and so accumulate PTMs over a lifetime. Eventually, a tipping point is reached when protein aggregation results in increased light scatter, inevitably leading to the iconic protein condensation–based disease, age-related cataract (ARC). Cataracts account for 50% of vision impairment worldwide, affecting far more people than other well-known protein aggregation–based diseases. However, because accumulation of crystallin PTMs begins before birth and long before ARC presents, we postulate that the lens protein PTMs contribute to a “cataractogenic load” that not only increases with age but also has protective effects on optical function by stabilizing lens crystallins until a tipping point is reached. In this review, we highlight decades of experimental findings that support the potential for PTMs to be protective during normal development. We hypothesize that ARC is preventable by protecting the biochemical and biophysical properties of lens proteins needed to maintain transparency, refraction, and optical function.

Citation

Quinlan, R. A., & Clark, J. I. (2022). Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens. Journal of Biological Chemistry, 298(11), Article 102537. https://doi.org/10.1016/j.jbc.2022.102537

Journal Article Type Article
Online Publication Date Sep 27, 2022
Publication Date 2022
Deposit Date Jan 30, 2023
Publicly Available Date Jan 30, 2023
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 298
Issue 11
Article Number 102537
DOI https://doi.org/10.1016/j.jbc.2022.102537
Public URL https://durham-repository.worktribe.com/output/1182009

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