# Mechanisms of Protein Aging in Normal and Cataractous Lenses

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2022 · $272,806

## Abstract

ABSTRACT
Cataract is the leading cause of blindness worldwide. Surgical removal of cataractous lenses
places an enormous financial burden on our economy and is not without side effects. Moreover,
the prevalence of cataract in the U.S. is expected to more than double by the year 2050.
Although new therapies are being developed to prevent or reverse early cataract, our
understanding of the underlying mechanisms of cataractogenesis remains unclear. The long-
term goals of our research are to identify modifications to lens proteins during aging and
cataractogenesis in order to define protein aging mechanisms and to develop ways to prevent,
delay, or reverse opacification. Recently, we have identified multiple age-dependent, non-
enzymatic biochemical processes that result in both age-related lens protein modification and
cataract-related lens protein crosslinking. The lens proteins and amino acids involved have
been identified; however, mechanistic details remain unresolved. In addition, we have observed
a dramatic re-distribution of soluble lens proteins to the membrane fraction in aged lens tissue.
Again, the operative mechanism(s) of this protein shift remains unknown. Our hypothesis is that
specific lens protein-protein crosslinks, peptide/lipid alterations, and crystallin binding to lens
membranes are cataractogenic. To test this hypothesis we will employ state-of-the-art imaging
mass spectrometry and proteomics/lipidomics methodology to further define age-related and
cataract-specific modifications and define conditions upon which the chemistry occurs to
determine chemical mechanism. Specifically we propose to: 1) define the protein sites and
chemistry of protein crosslinks in cataractous human lenses and, 2) define cataract-specific
peptide and lipid changes in human lenses, and 3) elucidate the molecular events that lead to
increased lens protein membrane binding with age and cataract formation. The proposed
experiments are expected to provide new mechanistic details on protein aging that will not only
inform the development of new cataract treatments, but also guide therapeutic development for
other aging and protein aggregation diseases.

## Key facts

- **NIH application ID:** 10386818
- **Project number:** 5R01EY024258-08
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Kevin L Schey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $272,806
- **Award type:** 5
- **Project period:** 2014-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386818

## Citation

> US National Institutes of Health, RePORTER application 10386818, Mechanisms of Protein Aging in Normal and Cataractous Lenses (5R01EY024258-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10386818. Licensed CC0.

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