# Pharmacological studies of rhodopsin metabolism

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $352,125

## Abstract

Summary: Genetic mutations of the dim-light visual pigment, rhodopsin (Rho), cause retinitis pigmentosa (RP),
and no effective pharmacological treatment is available for this inherited retinal degeneration. Our long-term
goal is to determine the molecular events that contribute to photoreceptor death in RP and develop effective
small molecule drugs targeting these events that preserve the retinal structure and visual function. Rho protein
misfolding causes rod cell death in RP. Our central hypothesis is: small molecules that stabilize Rho structure,
or those induce degradation of misfolded Rho can mitigate Rho-associated adRP. We recently discovered two
novel and potent lead compounds: 1) YC-001, a non-retinal chaperone of Rho that rescues folding of multiple
misfolded Rho mutants that cause RP; and 2) a U.S. Food and Drug Administration (FDA)-approved drug that
induces misfolded Rho degradation in vitro, and that possesses potent anti-inflammatory activity. Using the
well-studied Rho P23H knock-in mouse model of RP, we will determine the efficacy, mechanism of action, and
safety of these two compounds firstly in the isolated retinae explant culture, and then in vivo by an intravitreal
injection of YC-001 encapsulated in a controlled drug release formula, or via intermittent intravitreal injections
of the FDA-approved drug with optimized intervals. We will utilize state-of-the-art retinal imaging and
electrophysiology techniques to evaluate the retinal structure and visual function. We will conduct biochemical
and transcriptome analyses to identify the drug targeting pathways that regulate rhodopsin homeostasis. The
results from this study will provide comprehensive pharmacological profiles of the two lead compounds in a
rodent model of adRP, from which we will build a clear molecular network connecting rhodopsin expression,
folding, degradation and retinal inflammation with the progression of retinal degeneration and we will assess
the efficacy of these compounds as potential treatments for RP.

## Key facts

- **NIH application ID:** 10051702
- **Project number:** 1R01EY030991-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yuanyuan Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,125
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051702

## Citation

> US National Institutes of Health, RePORTER application 10051702, Pharmacological studies of rhodopsin metabolism (1R01EY030991-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051702. Licensed CC0.

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