# Retinal amino acid transport in health and disease

> **NIH NIH P20** · WEST VIRGINIA UNIVERSITY · 2024 · $303,997

## Abstract

Lysosomes play a critical role in cellular metabolism, acting not only as catabolic hubs but also as the site 
of nutrient sensing and metabolic signaling. Lysosomal dysfunction has been implicated in the blinding 
disease retinitis pigmentosa. Mutation and deletion of lysosomal arginine transporters, including solute 
carrier family 7 member 14 (SLC7A14), have been reported as causative genes for autosomal recessive 
retinitis pigmentosa. However, it is currently not known how dysregulation of lysosomal arginine 
metabolism causes vision loss. Our long-term objective is to determine how SLC7A14 mutations cause 
blindness and the role for SLC7 A 14 in vision. The objective of this application is to determine the function 
of SLC7A14 in endosomes/lysosomes and how mutation of SLC7A14 causes retinitis pigmentosa. The 
significance of these studies includes resolving current fundamental questions on cellular 
compartmentalization of metabolism as well as development of strategies for therapeutic approaches 
targeting dysregulated metabolism in diseases. Our central hypothesis is that SLC7 A 14-dependent 
lysosomal storage of cationic amino acids is essential for photoreceptor health. We will test this hypothesis 
by determining and validating the cell type responsible for SLC7A14-mediated retinitis pigmentosa (Aim 1) 
and by investigating the function and regulation of cationic amino acid transport by SLC7A14 (Aim 2). In 
Aim 1, we will use mouse models to determine the cell type responsible for the pathogenesis of SLC7 A 14- 
dependent vision loss, which is currently not known but is critical to understand disease pathology and 
progression. We will test our hypothesis that loss of expression of SLC7 A 14 in horizontal and/or bipolar 
cells causes retinitis pigmentosa. In Aim 2, we will use elucidate SLC7A14 transport kinetics and regulation 
using cell lines and recombinant protein. We hypothesize that SLC7A14 aids in lysosomal storage of amino 
acids to buffer cellular levels of cationic amino acids in times of amino acid scarcity. The outcomes of 
studies will provide mechanistic insight into SLC7A14 function, which is essential to understanding the 
function of SLC7A14 in the cell and how its dysregulation contributes to vision loss.

## Key facts

- **NIH application ID:** 10773201
- **Project number:** 5P20GM144230-03
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Bradley A Webb
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $303,997
- **Award type:** 5
- **Project period:** 2022-03-20 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773201

## Citation

> US National Institutes of Health, RePORTER application 10773201, Retinal amino acid transport in health and disease (5P20GM144230-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10773201. Licensed CC0.

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