# Photoreceptor Regeneration in a Murine Model of Leber Congenital Amaurosis

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2020 · $233,075

## Abstract

PROJECT TITLE
Photoreceptor Regeneration in a Murine Model of Leber Congenital Amaurosis
ABSTRACT
Leber congenital amaurosis (LCA) is an early-onset, severe inherited retinal degeneration that results in
childhood blindness. Gene therapy can effectively restore visual function in the Lca5gt/gt mouse model of the
disease when delivered to neonatal mice before significant retinal degeneration is present. However, in
moderate- and late- stage disease after photoreceptor cell death has occurred, gene therapy is no longer
effective. Cell-based therapies hold great promise for regenerating photoreceptors in late-stage retinal
degenerations, but progress has been limited by low efficiencies of integration and complex cellular
interactions with existing retinal cells.
Photoreceptor precursors represent a heterogeneous pool of diverse cells types that have the potential to
differentiate into mature photoreceptor cells in the developing and diseased retina. Using unbiased single-cell
RNA transcriptomics, I identified several novel populations of Crx+ photoreceptor precursors including
Crx+/Nfix+ and Crx+/Slc39a1+ cells. The scientific objectives of this proposal are to regenerate
photoreceptors in the Lca5gt/gt mouse model of retinal degeneration, by the transplantation of these novel
populations of photoreceptor precursors and by the activation of endogenous repair pathways in Müller glia.
The Aims of the proposal are 1) Subretinal transplantation of Crx+/Nfix+ and Crx+/Slc39a1+ progenitor cells in
Lca5gt/gt mice, and 2) Activation of endogenous Müller glial repair pathways by gene therapy in Lca5gt/gt mice.
In addition to these scientific contributions, this proposal outlines a structured, focused training plan that will
equip me with the skills and expertise that will serve as the foundation for my career in developing cell-based
therapies for retinal disease. The Department of Ophthalmology at the University of Pennsylvania is an ideal
environment for training physician scientists in ophthalmic research, and will provide the protected time,
resources, and mentorship needed for a successful transition to independence.

## Key facts

- **NIH application ID:** 10039360
- **Project number:** 1K08EY031754-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Katherine E. Uyhazi
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $233,075
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039360

## Citation

> US National Institutes of Health, RePORTER application 10039360, Photoreceptor Regeneration in a Murine Model of Leber Congenital Amaurosis (1K08EY031754-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10039360. Licensed CC0.

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