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Identification of Age- and Cataract-Related Changes in High-Density Lens Protein Aggregates
Zhen Wang1, Michael G Friedrich2, Roger J W Truscott2
1Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States.
Investigative Ophthalmology & Visual Science
|May 23, 2025
Summary
Cataract formation involves protein aggregation on eye lens membranes. Cataractous lenses show distinct modifications in gamma-crystallins within these aggregates, suggesting increased protein degradation contributes to the condition.
Area of Science:
- Ophthalmology
- Biochemistry
- Proteomics
Background:
- Cataract is linked to protein aggregation within the eye lens.
- Crystallins bind extensively to lens cell membranes with age.
- Protein modifications are associated with both aging and cataract formation.
Purpose of the Study:
- To characterize proteins and their modifications in high-density fractions of normal aged and cataractous lenses.
- To compare protein constituents and alterations between normal and cataractous lens membrane aggregates.
Main Methods:
- Proteins from cataractous and age-matched normal lenses were isolated using sucrose density gradient centrifugation.
- Proteomic analysis involved top-down MALDI-MS and bottom-up LC-MS/MS.
- Quantification of crystallin peptides, deamidation, and isomerization was performed.
Main Results:
- Cataract lens membrane aggregates had higher levels of gamma-crystallins and specific C-terminal peptides compared to normal lenses.
- Deamidation of gamma-crystallin, but not beta-crystallin, was elevated in cataractous aggregates.
- Asp isomerization was high in alpha-crystallins from both aged and cataractous lenses.
Conclusions:
- Crystallin aggregate binding to lens membranes involves truncation, deamidation, and isomerization.
- These modifications occur in both aged and cataractous lenses.
- Distinct gamma-crystallin modifications in cataract lenses suggest a role for enhanced protein degradation.