# Identifying Shared Pathogenic Networks and Molecular Targets Underlying Retinal Pigmented Epithelial Associated Disease

> **NIH NIH R01** · JACKSON LABORATORY · 2020 · $591,579

## Abstract

PROJECT SUMMARY
The long-term goal of the proposed project is to enable development of improved treatments for retinal pigment
epithelium (RPE) diseases. The RPE plays a critical role in function and maintenance of the posterior eye, and
RPE disruption can lead to severe vision impairment and loss. Many heritable retinal diseases have origins or
contributions from the RPE, including monogenic diseases and age-related macular degeneration, a complex
disease that is a leading cause of blindness in the western aging population. While gene augmentation therapy
has previously been used to successfully treat a small number of affected individuals with RPE-associated
diseases, currently there are no effective cures for the vast majority of these diseases. Hence, there is a
significant need to develop generalized therapeutic approaches that would be effective in treating multiple
RPE-related diseases. We have observed that numerous RPE disease phenotypes are shared among mouse
models bearing mutations in cell-adhesion and extracellular matrix (ECM) molecules, suggesting that the
underlying pathways/networks that are disrupted and lead to the observed pathologies might also be
shared. The goal of this project is to identify the common RPE pathogenic pathways/networks that may serve
as druggable targets. Identifying druggable targets that participate during the pre-symptomatic stage of the
disease is particularly important, to enable development of therapies that can prevent, delay onset, or
decrease the severity of RPE-associated diseases irrespective of the initial cause of the disease. Our
approach is to use four mouse models with RPE-driven disease to generate comprehensive quantitative
phenotypic data and global and single-cell gene-expression data, and to integrate and analyze these data
using sophisticated computational methods to reveal the shared molecular and biological mechanisms
associated with pre-clinical RPE pathology. This will be accomplished in three aims: 1) Assess pre-clinical and
end-stage RPE-related phenotypes in the four models. 2) Identify the shared molecular and biological
pathways underlying the RPE-related phenotypes in the four models. Global and single-cell gene expression
analysis will be performed, and these data and the phenotype data from Aim 1 will be analyzed using
computational methods to identify the shared pathways perturbed in the four models. The computational
results will be verified in vivo via generation and analysis of mouse models of key shared misregulated
molecules. These well-characterized models will be made available to the research community. 3) Further
validate in vivo that the phenotypes and key molecules and pathways identified in Aims 1 and 2 are similarly
perturbed in additional models bearing mutations in cell-adhesion and ECM molecules generated by the
KOMP2 program sited at The Jackson Laboratory (JAX). Successful completion of these aims will identify
common molecular and biological pathways und...

## Key facts

- **NIH application ID:** 9929017
- **Project number:** 5R01EY027860-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Gregory W Carter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $591,579
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929017

## Citation

> US National Institutes of Health, RePORTER application 9929017, Identifying Shared Pathogenic Networks and Molecular Targets Underlying Retinal Pigmented Epithelial Associated Disease (5R01EY027860-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9929017. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*