# Wiring specificity and plasticity of rod and cone photoreceptor circuits

> **NIH NIH K99** · UNIVERSITY OF WASHINGTON · 2020 · $105,356

## Abstract

PROJECT SUMMARY/ABSTRACT
The retina generates rod and cone photoreceptors with distinct light sensitivity and synaptic connectivity to
execute night- and day-time vision, respectively. Disruption of particular transcription factors affect
photoreceptor differentiation during development and the maintenance of photoreceptor-specific properties in
the adult. For instance, loss of Neural Retina Leucine zipper (NRL) or Nuclear Receptor Subfamily 2 Group E
Member 3 (NR2E3) in mouse retina transform cells with rod-fate into cone-like cells, at embryonic or adult
stages. Rod->cone transformations have been found to protect photoreceptors from degeneration in mice with
certain retinal diseases. However, it is unclear whether and how transformed photoreceptors wire with their
downstream target neurons, particularly bipolar cells (BCs), to convey visual signals. Rod->cone
transformations in some retinal diseases can, however, compromise visual function. The possibilities of
reversing such photoreceptor transformations, restoring proper connectivity and re-establishing normal visual
function are unknown. To advance knowledge in these areas, this proposal will determine the connectivity
patterns of BCs with transformed photoreceptors under different conditions. A combination of
immunohistochemistry, electron microscopy, and electrophysiology will be used to examine mice with
photoreceptor transformation at different ages and to different extents. In Aim 1, mice with Nrl deletion at
embryonic (Nrl-/-) and adult (NrlCKO) stages will be used to determine the connectivity between BCs and cones
or cone-rod hybrids derived from rod-fated cells at different ages. In Aim 2, rd7 mice, which model human
retinal disease with mutations in Nr2e3, will be used to further assess BC wiring with cones and cone-rod
hybrids transformed from rod precursors. Restoration of normal rod/cone ratios in adult rd7 will be attempted,
using adeno-associated viruses (AAVs) to drive NR2E3 expression in transformed photoreceptors. The results
will indicate the possibility of rod restoration in adult rd7, as well as the plasticity of the mature retina in
recovering disrupted circuitry. In both aims, the visual responses of BCs or ganglion cells will be investigated to
assess the impact on visual function by photoreceptor transformation and restoration. Overall, the knowledge
gained from this proposed study will not only advance our understanding of the cellular mechanisms underlying
photoreceptor type-specific connectivity, but also provide insights into designing future retinal repair strategies.
The applicant will receive training from Drs. Rachel Wong (primary mentor), Thomas Reh and Fred Rieke at
the University of Washington to attain the essential knowledge, techniques and professional skills to pursue an
independent research career dedicated to discovering the basic mechanisms that regulate neural circuitry
assembly and repair.

## Key facts

- **NIH application ID:** 9868205
- **Project number:** 1K99EY030898-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Chi Zhang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $105,356
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868205

## Citation

> US National Institutes of Health, RePORTER application 9868205, Wiring specificity and plasticity of rod and cone photoreceptor circuits (1K99EY030898-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868205. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*