# Probing the molecular basis of refractive index in lens proteins

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $179,245

## Abstract

Project Summary
The vertebrate eye lens is made up of concentrated, highly refractive proteins called crystallins, which enable it
to form images by focusing light on the retina. Most studies of crystallins focus on their ability to remain stable
and soluble for decades in the absence of protein turnover in the lens. Refractivity is equally important to crystallin
functionality, but is less well understood. This project seeks to elucidate how crystallins provide focusing power
both as individual proteins and as a network of intermolecular interactions in the crowded environment of the
lens. Our preliminary work has shown that amino acid composition alone does not determine crystallin refractiv-
ity: three-dimensional structure and interactions with water on the protein surface are also critical. We will build
on this work by measuring the refractive index increment for lens crystallins from humans and model organisms
and relating the results to spatial interactions among polarizable side-chain moieties. In particular, we propose
to investigate cataract-related and engineered crystallin variants in order to test hypotheses about how structure
impacts refractivity. We will measure refractivity first in concentrated solutions mimicking the crowded cellular
milieu, and then in whole lenses from model organisms in order to set the stage for future studies on human
lenses. This will enhance the current model of protein refractivity, which is mostly based on measurements in
dilute solution. On the level of the whole lens, we will develop novel methodologies to specifically visualize the
refractive index distribution in space. The long-term goal of this research is to bridge the gap between interactions
of light with individual crystallin molecules and the spatial arrangement of proteins that generates the refractive
index gradient of the vertebrate lens. In the future, the knowledge gained will provide insight into healthy lens
function and guide the design of improved artificial lens materials.

## Key facts

- **NIH application ID:** 10791520
- **Project number:** 1R21EY035792-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Rachel Wagner Martin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $179,245
- **Award type:** 1
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791520

## Citation

> US National Institutes of Health, RePORTER application 10791520, Probing the molecular basis of refractive index in lens proteins (1R21EY035792-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10791520. Licensed CC0.

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