# Retinal structure, function and response to gene therapy

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $521,325

## Abstract

Project Summary
 The Food and Drug Administration's approval of Luxturna marked a new era in the fight to cure blindness
caused by inherited retinal degenerations (IRDs). However, despite an approved treatment for RPE65-
mediated disease, there are still over 280 molecularly distinct, currently untreatable IRDs that cause vision loss
from progressive death of the rod, cone, and retinal pigment epithelial (RPE) cells. Further, treatment with
Luxturna does not fully restore vision to normal levels in RPE65-mediated disease, particularly for foveal cone
vision, and there is variability between patients in the amount of vision gained post-treatment.
 Numerous therapeutic approaches, including gene therapies similar to Luxturna, are under development
for IRDs. To maximize chances of success, it is critical to understand the natural sequence of degeneration in
each disease, both to optimize the timing and retinal location of applied therapies as well as to enable precise
evaluation of whether the therapies had an effect.
 We will use multi-modal adaptive optics scanning light ophthalmoscopy (AOSLO) to simultaneously
observe the cone inner segment (IS) and waveguiding outer segment (OS) mosaics and RPE mosaics to
identify AO structural phenotypes in IRDs. We will also use AO microperimetry and optoretinography to test
photoreceptor function in the same IRD patients. Finally, we will measure the AO structural and functional
responses to Luxturna gene therapy for RPE65-mediated disease and AAV2.hCHM gene therapy for
choroideremia. Based on our preliminary and published data, we hypothesize that cone function correlates with
structural phenotype, cones exhibit dysfunction prior to their structural loss, gene therapy will slow or halt
structural degeneration, and gene therapy will reverse photoreceptor dysfunction at retinal locations where
cells are structurally intact but functionally compromised. The information gained through our studies will
enable cellular scale assessment of the safety and efficacy of gene therapy and the will validate AO cellular
scale outcome measures for use in future clinical trials.

## Key facts

- **NIH application ID:** 10803346
- **Project number:** 2R01EY028601-06
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jessica I.W. Morgan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $521,325
- **Award type:** 2
- **Project period:** 2018-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803346

## Citation

> US National Institutes of Health, RePORTER application 10803346, Retinal structure, function and response to gene therapy (2R01EY028601-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10803346. Licensed CC0.

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