# TRP-CHANNELS IN LENS DEVELOPMENT AND CATARACT

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $369,443

## Abstract

Project Summary/Abstract
The transient receptor potential (TRP) superfamily of non-selective cation channels play critical roles in diverse
physiological processes including the perception of light, temperature, pressure, and pain. In previous genetic
studies, we have discovered that mutation of a member of the melastatin-related TRP-channels (TRPM3)
underlies an inherited form of pediatric cataract that is variably associated with glaucoma and anterior segment
defects. In this proposal, we will investigate the role of TRPM3 in lens development and cataract pathobiology
using gene-edited mice and cell-lines by addressing three specific aims. In aim-1, we will characterize lens
TRP-channel transcript splice-variants by means of RNA deep-sequencing and the calcium channel properties
of lens TRPM3 isoforms using fluorometric calcium imaging techniques. In aim-2, we will characterize the
effects of TRPM3 dysfunction and deficiency on lens cation status, water content, and calcium influx properties
using a combination of atomic absorption spectrometry and calcium imaging techniques. In aim-3, we will
characterize the effects of TRPM3 dysfunction and deficiency on lens morphogenesis and gene expression
using differential immuno-fluorescence microscopy and RNA deep-sequencing techniques, respectively.
Results from these studies will provide new insights regarding the role of TRP-channels in lens growth, cation
homeostasis, calcium dynamics, and pathophysiology within the context of pediatric cataract – a clinically
important risk factor for lifelong visual impairment. More broadly, these studies will contribute to an
understanding of TRP-channel function and dysfunction in other eye tissues (e.g., iris, ciliary body) and
diseases (e.g., glaucoma, anterior eye defects), respectively.

## Key facts

- **NIH application ID:** 10327301
- **Project number:** 5R01EY028899-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Alan Shiels
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $369,443
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327301

## Citation

> US National Institutes of Health, RePORTER application 10327301, TRP-CHANNELS IN LENS DEVELOPMENT AND CATARACT (5R01EY028899-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10327301. Licensed CC0.

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