# Melanopsin-dependent light-evoked development of rod photoreceptors

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $401,250

## Abstract

It has been known for some time that development of the visual system can be an adaptive
process in which light exposure or visual experience modifies the final structure. Here we
propose to investigate a developmental pathway in which photoreception via OPN4 in
intrinsically photosensitive retinal ganglion cells (ipRGCs) regulates rod photoreceptor
survival. Preliminary data show that light and OPN4 regulate rod precursor cell death in the
neonatal retina and rod number in adult mice. This is mediated by the neuromodulator glutamate.
We suggest that ipRGC outer retinal dendrites (ORDs) deliver glutamate to the outer retina and
regulate rod survival. ORDs are unique to ipRGCs and are transient, existing only during the first
week after birth. Single cell sequencing data reveal that the glutamate receptor Grik3 is expressed
in rod precursors transiently in the first week after birth and is thus a good candidate to mediate
this response. These data suggest the Central Hypothesis that Perinatal light sensing by
ipRGCs regulates rod photoreceptor number via glutamate-induced precursor cell death.
We propose three Aims designed to define the mechanisms underlying this proposed adaptive
response. We will define the developmental time-course of ORDs and assess markers of
glutamate function (Aim 1), assess the proposed relationships in the light-OPN4-Gαq-rod cell
death pathway (Aim 2), and assess glutamate delivery by ipRGC ORDs and the response of rod
precursors (Aim 3). The finding that early developmental light sensing regulates the number
of rod photoreceptors is unexpected and of broad interest because it represents a novel
mechanism and has implications for human eye development.

## Key facts

- **NIH application ID:** 10931631
- **Project number:** 5R01EY034456-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Richard A. Lang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,250
- **Award type:** 5
- **Project period:** 2023-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931631

## Citation

> US National Institutes of Health, RePORTER application 10931631, Melanopsin-dependent light-evoked development of rod photoreceptors (5R01EY034456-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931631. Licensed CC0.

---

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