# Retina Differential Gene Expression Modifiers that affect Vision

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $35,733

## Abstract

Project Summary:
Inherited retinal diseases (IRDs) are a major cause of blindness in the working adult population and present an
enormous emotional and socioeconomic burden on patients and their families. Mutations in almost 200 genes
have been shown to cause IRDs, however, no treatment options are currently available to prevent disease
onset, increase visual function, or delay vision loss. One major challenge in the development of effective
treatment strategies is the heterogeneity of clinical presentation in these diseases. This phenotypic variation in
presentation is likely due to genetic variation between individuals, even those within the same family. One
possible explanation for the variation are genetic modifiers that interact with the disease-causing gene. Genetic
modifiers have been discovered in many diseases and can influence many aspects including disease onset,
severity, and progression. Many IRD-causing mutations affect genes involved in RNA processing and due to
the high metabolic needs of specialized retinal cell types, such as photoreceptors, the retina is particularly
sensitive to aberrant RNA processing. Our lab has implicated a 0.3Mb region on mouse chromosome 4 that
controls the differential expression of ~170 exons in genes located throughout the genome in 55 recombinant
inbred mouse strains. The exons have a dichotomous expression pattern in the parental strains, C57BL/6J and
DBA/2J, with a particular exon having relatively high expression in C57BL/6J and relatively low expression in
DBA/2J. The premise of this proposal is to identify the gene located in this 0.3Mb region that controls this
Mendelian-like inheritance pattern phenotype. Lsd1 is one of six genes found in the 0.3 Mb locus, and it
exhibits four nonsynonymous changes between C57BL/6J and DBA/2J. Four of the other genes in the locus
lack any nonsynonymous changes and are low priority. Lsd1 is our top priority candidate as it has functions in
the terminal differentiation of rods and cones. We hypothesize that Lsd1, a known epigenetic regulator and
transcriptional corepressor in the developing retina, controls this differential exon expression and is a genetic
modifier of IRDs. We will determine whether Lsd1 is controlling differential expression in adult mice by
performing microarray analysis on Lsd1 conditional knock out mice andtransgenic Lsd1 classic knockout mice.
Additionally, we will assess whether histone code differences between C57BL/6J and DBA/2J are the
mechanism underlying the differential expression in adult retina.

## Key facts

- **NIH application ID:** 10001521
- **Project number:** 5F31EY028855-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Salma Ferdous
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,733
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-04-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001521

## Citation

> US National Institutes of Health, RePORTER application 10001521, Retina Differential Gene Expression Modifiers that affect Vision (5F31EY028855-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10001521. Licensed CC0.

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