# Comparative Single Cell Profiling of Retinal Development

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2021 · $46,036

## Abstract

Project Summary
Age-related macular degeneration (AMD) affects the central region of the retina important for high-acuity
daytime vision, causing blindness or severe vision impairment as a result of the loss of photoreceptors from the
cone-dominant fovea. Directed differentiation of retinal progenitor cells into cone photoreceptors shows
promise as a therapy for AMD and other retinal dystrophies. However, commonly used model organisms such
as the mouse have rod-dominant retinas, which makes them poor models for the human fovea. 13-lined
ground squirrel retinas, however, have a cone/rod ratio and cone subtype composition that closely matches
that of the human fovea. This project will use the 13-lined ground squirrel as a model to identify gene
regulatory networks that drive development of retinal cones and test whether gain of function of candidate
genes can promote cone development in mice. I hypothesize that differential activation of gene regulatory
networks controlling photoreceptor development underlie the differences in the cone/rod ratio between
the mouse and 13-lined ground squirrel and between the peripheral human retina and the cone-
dominant fovea. To address this hypothesis, I propose two Aims. Aim 1: Comprehensively profile retinal
development in the 13-lined ground squirrel at single-cell resolution using both scRNA-seq and scATAC-seq to
identify candidate gene regulatory networks that control evolutionary changes in the cone/rod photoreceptor
ratio. This data will allow me to identify key gene regulatory networks that control development of the 13-lined
ground squirrel retina and will identify plausible causes for the difference in the production of photoreceptor
subtypes between 13-lined ground squirrel and mouse and between the fovea and peripheral human retina.
Aim 2: Test the functional consequences of overexpression of candidate genes in mice that are predicted to
promote cone specification in 13-LGS. This will identify which changes are necessary to control the cone/rod
ratio in the developing mouse retina. By understanding the gene regulatory networks that control photoreceptor
proportions in the retina, I will be able to direct mouse retinal progenitors to generate a cone-dominant retina,
ultimately providing an improved animal model for AMD progression and cell therapy.

## Key facts

- **NIH application ID:** 10231701
- **Project number:** 1F31EY031942-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kurt L Weir
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-05-03 → 2023-05-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231701

## Citation

> US National Institutes of Health, RePORTER application 10231701, Comparative Single Cell Profiling of Retinal Development (1F31EY031942-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10231701. Licensed CC0.

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