# Functional plasticity in retinal degenerative disease

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $385,000

## Abstract

During the last two decades it has become clear that the retina is not just a static network of neurons. Retinal
neurons change their properties and connections during aging or disease in a process termed retinal remodeling
or plasticity. However, mechanisms that mediate plasticity, as well as the impact of plasticity on light signaling in
the retina and vision are still poorly defined. Our long-term goal is to advance the field of retinal remodeling
towards development of vision restoration therapies with improved outcomes. This goal is achieved by (i)
determining compensatory mechanisms in the retina that can promote vision, and (ii) quantifying the impact of
remodeling on the retinal output and vision during photoreceptor degenerative disease. Our central hypothesis
is that a partial loss of sensory input from rods increases the gain of transmission of the remaining input to rod
bipolar cells (RBCs) in the retina to promote vision, whereas extensive loss of the sensory input leads to a
corruption of the light signal transmission and exacerbation of vision loss. This central hypothesis will be tested
in a mouse model of autosomal dominant retinitis pigmentosa caused by the rhodopsin P23H mutation. The
rationale of this project is that delineating a compensatory mechanism in the retina will yield an accessible target
for promoting vision in photoreceptor degenerative diseases where this does not happen naturally. Secondly,
new knowledge about the impact and time course of constructive and destructive remodeling in the retina on
vision will generate critical information about the expected outcomes of vision restoration therapies. The central
hypothesis will be tested in two specific aims: 1) Determine the mechanism underlying the increase of rod - RBC
signal transmission at early stages of retinal degenerative disease; and 2) Determine the impact of inner retinal
remodeling on light signal transmission during photoreceptor degenerative disease. In the first aim, a working
hypothesis that rod – RBC transmission is potentiated in P23H mice via synaptotagmin-1 (Syt1)-dependent
pathway in rod synaptic terminal will be tested by using P23H mice with a rod-specific deletion of Syt1 and in
vivo/ex vivo Electroretinogram as well as patch clamp physiology. In addition, these mice will be used to
determine the impact of this compensatory mechanism on vision using behavior methods. In the second aim,
genetic silencing of photoreceptors and optogenetics will be used together with ganglion cell multielectrode array
electrophysiology in P23H mice to evaluate the impact of inner retina remodeling on ganglion cell output during
photoreceptor degeneration from early to late-stage disease. This innovative work 1) challenges current dogma
of destructive remodeling by asserting that in some retinal degenerative diseases, the retina compensates for
the loss of photoreceptors to maintain stable output and vision; and 2) applies genetic and optogenetic tools to
determi...

## Key facts

- **NIH application ID:** 10831433
- **Project number:** 5R01EY034986-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Frans Vinberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831433

## Citation

> US National Institutes of Health, RePORTER application 10831433, Functional plasticity in retinal degenerative disease (5R01EY034986-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10831433. Licensed CC0.

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