# Elucidating the molecular mechanisms of secondary cone degeneration in models of Retinitis Pigmentosa

> **NIH EY R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2026 · $663,406

## Abstract

Project Summary
Retinitis Pigmentosa (RP) is an inherited retinal disease afflicting 1 in 4,000 people worldwide. The disease
progresses initially by rod photoreceptor degeneration caused by mutations in rod-specific genes, although
different mutations in different genes converge upon the same rod degeneration phenotype in this disease.
However, it is the subsequent cone photoreceptor degeneration that causes loss in daylight color vision and,
ultimately, diminishing quality of life for most patients. While gene therapy to replace a mutated gene with a
functional copy has been successful, given the heterogeneity of mutations and genes, treating all RP cases by
targeting the rods is difficult. Instead, a generic therapy to preserve the cones upon rod degeneration may lead
to a more comprehensive therapeutic option. Previously, we discovered that activation of the Retinoic Acid
signaling pathway is sufficient to promote cone survival in a mouse model of RP. To further develop this signaling
pathway as a potential gene-agnostic therapeutic for all patients with RP, we will develop a novel AAV-based
Retinoic Acid signaling activator to test whether it can improve photopic visual acuity in multiple mouse models
of RP. Furthermore, using this signaling pathway as a molecular handle, we will aim to elucidate the molecular
and cellular mechanisms downstream of this signaling pathway that contribute to the cone survival effect.

## Key facts

- **NIH application ID:** 11271215
- **Project number:** 1R01EY038190-01
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Ryoji  Amamoto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** EY
- **Fiscal year:** 2026
- **Award amount:** $663,406
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11271215

## Citation

> US National Institutes of Health, RePORTER application 11271215, Elucidating the molecular mechanisms of secondary cone degeneration in models of Retinitis Pigmentosa (1R01EY038190-01). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11271215. Licensed CC0.

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