# Retinal Circuitry Response to Nerve Injury

> **NIH NIH F31** · YALE UNIVERSITY · 2023 · $47,694

## Abstract

Project Summary/Abstract
Healthy vision requires the function of parallel cellular and synaptic pathways in the neural retina. Circuits
constructed from diverse cell types provide the anatomical and physiological basis for encoding diverse visual
scenes. Indeed, visual inputs to the mouse retina are converted to electrical signals by photoreceptors (1 rod, 2
cone types), integrated by interneurons (1 horizontal, ~15 bipolar, ~60 amacrine cell types), and relayed to the
brain by retinal ganglion cells (>40 types) whose axons form the optic nerve. In a surgical model of nerve
injury, called the optic nerve crush (ONC), the axons of retinal ganglion cells (RGCs) are damaged. In
response to ONC, 70-80% of RGCs die within two weeks. The death of RGCs is biased, however, and
depends on the RGC type. A group of resilient RGC types persists and survives for weeks following the crush,
whereas other susceptible RGC types die within a few days. A long-term goal of the ONC model is to rescue
injured RGCs and enable regrowth of axons to target brain regions and restore functional vision. The field has
identified transcriptomic and tissue-level mechanisms that promote RGC survival. Furthermore, RGC survival
and axon regeneration are enhanced by RGC electrical activity (e.g., action potential firing). However, there is
a major gap in our understanding of (1) how activity of different RGC types is affected following ONC; (2) how
changes in activity align with the resilient/susceptible category of RGC types; and (3) whether there are cellular
or synaptic mechanisms that are affected by ONC and prohibit the ability to enhance activity in certain RGC
types following injury. I will therefore utilize electrophysiological and confocal microscopy techniques to
directly address my hypothesis that dysfunction and reduced firing in RGCs post optic nerve crush
depends on the RGC type and reflects a combination of synaptic and cell-intrinsic mechanisms. I will
measure the anatomy and physiology of specific RGC types that are either resilient or susceptible to ONC and
determine the contributions of either synaptic or intrinsic mechanisms to RGC hypoactivity after ONC.
Understanding these mechanisms will generate insights into how naturally-occurring diseases that affect the
optic nerve, such as glaucoma, cause dysfunction and death of RGCs and could contribute to the design of
rational therapies.

## Key facts

- **NIH application ID:** 10751621
- **Project number:** 1F31EY034776-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Thomas Eugene Zapadka
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-09-07 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751621

## Citation

> US National Institutes of Health, RePORTER application 10751621, Retinal Circuitry Response to Nerve Injury (1F31EY034776-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10751621. Licensed CC0.

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