# Approaches to enhance lysosomal function in RPE cells

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

Project Summary
Chloroquine retinopathy is a growing health problem with the increased use of the drug to treat lupus and
rheumatoid arthritis. Patients present with a loss of central vision, retinal pigmented epithelium abnormalities,
and bull’s eye maculopathy. There is currently no treatment other than to stop giving chloroquine; this limits the
long-term treatment of the other diseases, and the retention of chloroquine in pigmented tissues enables
progressing loss of vision even after treatment has stopped. While is known to target RPE lysosomes and
impair their degradative activity, it remains unclear how this leads to vision loss and how this can be treated.
Recently, lysosomes have been identified as playing a critical role in intracellular and extracellular signaling,
with lysosomal function extending beyond degradation to calcium signaling and the exocytosis of waste,
transmitters and inflammatory signals. This proposal will determine whether these newly identified lysosomal
functions are perturbed in chloroquine retinopathy. The ability of chloroquine treatment to alter lysosomal
calcium signaling and exocytosis will be assayed first in our in vitro model of chloroquine retinopathy, then
confirmed in our newly developed in vivo murine model of chloroquine retinopathy. The proposal will then
determine whether treatments developed in recent years to enhance lysosomal pH and calcium regulation
prevent the pathological changes induced by chloroquine. The restoration of lysosomal function will be
determined using both in vitro and in vivo models. Finally, the ability of these treatments to prevent the loss of
vision and photoreceptors in the chloroquine retinopathy mouse will be determined. The results of the project
will advance our mechanistic understanding of RPE signaling in health and disease while potentially helping
answer a real health need.

## Key facts

- **NIH application ID:** 10013212
- **Project number:** 5R01EY013434-16
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** CLAIRE H MITCHELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2002-02-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013212

## Citation

> US National Institutes of Health, RePORTER application 10013212, Approaches to enhance lysosomal function in RPE cells (5R01EY013434-16). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10013212. Licensed CC0.

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