# Interaction of alpha-crystallin with cholesterol bilayer domains in cataract formation

> **NIH NIH R01** · BOISE STATE UNIVERSITY · 2021 · $292,596

## Abstract

PROJECT SUMMARY/ABSTRACT
The objective of this proposal is to understand the interaction of α-crystallin with membrane cholesterol (Chol)
and cholesterol bilayer domains (CBDs) in the fiber-cell plasma membranes of the human eye lens. CBDs are
formed in the fiber-cell plasma membrane of the eye lens and have positive physiological functions, helping to
maintain lens transparency and possibly protect against cataract formation. The soluble lens protein, α-crystallin,
is a major structural protein that, under healthy conditions, forms a transparent lattice in the lens and plays a
major role in maintaining lens transparency. Several discoveries report that the level of α-crystallin in the lens
cytoplasm declines with age and cataract progression, accompanied by a corresponding increase in the amount
of membrane-bound α-crystallin. However, the mechanism by which α-crystallin associates with fiber-cell plasma
membrane and how the age-related change in membrane lipid composition affects the α-crystallin binding is
unclear. I hypothesize that the binding of α-crystallin to membrane is inhibited by CBDs, which decreases the
light scattering and helps maintain lens transparency. In their proposed role, CBDs should increase the level of
α-crystallin in the lens cytoplasm favoring its chaperone function and maintaining lens cytoplasm homeostasis. I
discovered that the properties of CBDs change significantly with age and are related to the size of the CBD,
which increases with age and is greater in nuclear than in cortical membranes. Based on my extensive
experience working with CBDs in model and human lens membranes, I will (i) determine the lipid composition in
fiber-cell plasma membranes that promotes or inhibits the binding of α-crystallin to membranes, (ii) test the
hypothesis that CBDs inhibit the binding of α-crystallin to membranes, and finally (iii) determine the effects of
CBD on the binding of α-crystallin in clear and cataractous human lens membranes of different age groups. The
analysis will include donor's health history, sex, and race. I developed electron paramagnetic resonance (EPR)
methods to study small-volume aqueous biological samples (3 µL at X-band or 150 nL at W-band), particularly
for studies of lens membranes obtained from the eyes of a single donor. This technique provides a major
advantage when studying the binding of α-crystallin in membranes of age-matched clear and cataractous lenses
from human donors. In addition, the EPR approach has the unique ability to simultaneously provide information
about the CBDs and the binding of α-crystallin. For the last eight years, my research has focused on
understanding the molecular organization of lipids and proteins in plasma membrane of intact fiber cells of human
eye lenses. Building upon the knowledge I acquired during these studies, here I propose moving my research in
a new direction to focus on the interaction of CBDs with α-crystallin. There is a clear need for a more in-depth
under...

## Key facts

- **NIH application ID:** 10186757
- **Project number:** 5R01EY030067-03
- **Recipient organization:** BOISE STATE UNIVERSITY
- **Principal Investigator:** Laxman Mainali
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $292,596
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186757

## Citation

> US National Institutes of Health, RePORTER application 10186757, Interaction of alpha-crystallin with cholesterol bilayer domains in cataract formation (5R01EY030067-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10186757. Licensed CC0.

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