# Retinal Disease: Molecular Basis and Pathophysiology

> **NIH NIH R01** · JACKSON LABORATORY · 2024 · $703,969

## Abstract

PROJECT SUMMARY/ABSTRACT
 Understanding how a pathogenic mutation leads to disease is extremely important for prognosis, for
developing effective treatments and for assessing likely response to treatment. Genes do not act in isolation.
Gene mutations typically do not cause the disease pathology themselves - rather, they activate or deactivate
biological pathways, affecting a set of molecules whose function results in the manifestation and progression of
disease phenotypes. Furthermore, evidence from several groups including our preliminary omics studies
suggests that alterations in different sets of molecules may lead to multiple disease phenotypes, further adding
to the complexities underlying genetic mutations and their effects.
 The goal of this application is to delve into this complexity by looking closely at three different disease aspects
of the Mfrprd6 mutation, namely, photoreceptor degeneration, hyperopia and fundus spotting, and examine their
association with three intermediary phenotypes, aberrant DHA levels, cytoskeletal derangements and immune
cell responses. Our approach is to use clinical, functional and biochemical tests to provide a deep
characterization of the disease phenotypes and to examine associated cellular changes using single-nuclear
transcriptomics and proteomic analyses. These phenotypic and genomics data will be analyzed using
computational methods to identify the earliest perturbations in these models, and to determine in proof-of-
principle experiments, whether it is possible to manipulate the disease outcomes with nutriceutical and
pharmacological interventions. Successful completion of our studies will identify the pathogenic pathways that
result in observed disease phenotypes, due to the disruption of Mfrp function, revealing potential therapeutic
targets that may play a role in a broad range of retinal genetic diseases with similar phenotypic manifestations.
.

## Key facts

- **NIH application ID:** 10827897
- **Project number:** 5R01EY011996-20
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Patsy M Nishina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $703,969
- **Award type:** 5
- **Project period:** 1998-02-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827897

## Citation

> US National Institutes of Health, RePORTER application 10827897, Retinal Disease: Molecular Basis and Pathophysiology (5R01EY011996-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10827897. Licensed CC0.

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