# Analyses of retinal circuits after rod rescue in a mouse model of human blindness

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $521,804

## Abstract

Project Summary
Rod photoreceptor death is a significant cause of human blindness, and much research effort has been
expended towards their rescue or replacement using gene or stem cell therapy. However, rod death is
followed by secondary changes in the inner retina such as dendritic remodeling, cell migration, and rewiring.
The extent to which this reorganization obstructs the potential for recovery of vision following photoreceptor
rescue is not known. The objective of this proposal is to examine signal processing in the affected retina
following the genetic rescue of rods. To this end, we have created a mouse model of retinal degeneration
caused by loss of expression of the β-subunit of the cyclic nucleotide-gated (CNGβ1) channel, a model for
autosomal recessive retinitis pigmentosa in humans. The novelty of this mouse model is that CNGβ1 can be
expressed from the endogenous locus in all affected CNGB1-/- rods upon tamoxifen(TX)-inducible Cre-
mediated recombination, leading to rod rescue. This proposal utilizes this mouse line to determine the impact
of rescuing rod function on retinal signal processing. In Aim 1 we will examine how the structure and function
of rod photoreceptors recovers following the restoration of CNGβ1 expression. In particular we will examine
the extent of functional recovery when TM is administered in mice with increasing severity of retinal
degeneration, as this may identify a critical window for the efficacy of rod recovery and halting further
degeneration. In Aim 2 we will examine how the synapse between rods and their primary postsynaptic partner,
rod bipolar cells, is reformed following rod rescue. Synapses between rods and rod bipolar cells form retinal
circuits that regulate our night vision. Finally, in Aim 3 we will evaluate how rod rescue impacts the function of
retinal ganglion cells, which are the sole conduit for signals from the retina to reach higher brain areas. The
central hypothesis is that while light sensitivity will recover substantially with rod rescue, some deficits in retinal
signaling will persist and worsen at late rescue ages due to secondary changes in retinal circuits. These
studies will define the window of opportunity for therapeutic intervention and provide a foundation for future
studies aimed at reversing the negative effects of neural remodeling.

## Key facts

- **NIH application ID:** 9994298
- **Project number:** 5R01EY027193-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jeannie Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $521,804
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994298

## Citation

> US National Institutes of Health, RePORTER application 9994298, Analyses of retinal circuits after rod rescue in a mouse model of human blindness (5R01EY027193-05). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/9994298. Licensed CC0.

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