# Mechanisms of altered neuronal activity in experimental glaucoma

> **NIH NIH R21** · YALE UNIVERSITY · 2024 · $460,625

## Abstract

Project Summary/Abstract
Healthy vision depends on multiple levels of processing in the retina, the neural tissue that lines the back of the
eye. Photoreceptors respond to light and drive signals in retinal interneurons. Interneurons converge onto the
retinal ganglion cells (RGCs), the retina's output neurons that project axons through the optic nerve to multiple
targets in the brain. All of our visual processing depends on signals generated by the RGCs. The RGCs
become injured and die in glaucoma, the leading cause of preventable and irreversible vision loss in humans.
A leading risk factor for the development of glaucoma is increased intraocular pressure (IOP). With increased
IOP, RGC axons become compromised as they exit the eye to form the optic nerve. Subsequent axon
degeneration and RGC death permanently impairs vision. We understand that RGC electrical activity can
influence RGC health, and it is known that RGC activity is compromised in mouse models of glaucoma,
following either elevations in IOP or direct injury to the optic nerve. Here, we will use two mouse models of
optic nerve injury (increased IOP and optic nerve crush) to investigate how these injuries impact RGC activity
and identify cellular and synaptic mechanisms underlying the changes in activity. Furthermore, we will consider
different categories of RGC types, which have dramatically different responses to glaucomatous injury.
Resilient RGCs survive glaucomatous insults well, while susceptible RGCs die quickly after injury. We will test
methods for controlling RGC activity in vivo and evaluate the impact of these manipulations on survival for
specific RGC types. The experiments will use patch clamp recording in an in vitro preparation of the mouse
retina at specific time points following RGC injury and will characterize specific RGC types that are either
resilient or susceptible to injuries. Specific Aims will (1) determine underlying cellular and synaptic mechanisms
that explain changes in RGC activity following each type of injury; and (2) validate methods for controlling
activity in injured RGCs and test their impact on RGC survival. The results will improve our understanding of
activity changes in specific RGC types following injury and will facilitate the development of future studies
aimed at modulating activity in vivo and improving the survival and regeneration of RGC signaling in human
glaucoma.

## Key facts

- **NIH application ID:** 10997737
- **Project number:** 1R21EY036705-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jonathan B Demb
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,625
- **Award type:** 1
- **Project period:** 2024-09-30 → 2026-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997737

## Citation

> US National Institutes of Health, RePORTER application 10997737, Mechanisms of altered neuronal activity in experimental glaucoma (1R21EY036705-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10997737. Licensed CC0.

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