# Retinal Ganglion Cell Signaling Regulated By Intrinsic Reactive Oxygen Species

> **NIH NIH R01** · DOHENY EYE INSTITUTE · 2024 · $392,500

## Abstract

Project Abstract
This proposal to investigate the impact of the bioenergetically-regulated, metabolic environment on the
sensitivity and signaling of retinal ganglion cells blends two converging lines of inquiry. The first arises from
evidence that neuronal metabolic stress is accommodated within diverse and complex solutions. The second
stems from our extensive knowledge of ganglion cell signaling functions, some of which we now interpret as
adaptions to the consequences of fluctuating energy requirements. The focus of this proposal is on identified
ganglion cell responses to light and how changes to specific response features are modulated by intrinsic
metabolic activity. There is a gap in our understanding of how the different response-forming functions of
cellular excitability may be changed during metabolic stress as well as the degree of the consequences of these
changes to ganglion cell sensitivity and visual function overall, especially during the pathological conditions
that lead to ganglion cell loss.
Our investigations will test hypotheses that intersect at the bioenergetic state of the retina and its effects on the
signaling of ganglion cells. In Specific Aim 1, we will define how the normal environmental conditions of the
outer retina contribute to the response features of ganglion cells. We will test the hypothesis that intrinsic
metabolic activity has a key influence on ganglion cell light responses by comparing controlled oxidant
modulation of the cells' response waveforms. In Specific Aim 2, we will characterize the oxidant sensitivity of
the cells' excitability mechanisms responsible for ganglion cell action potential generation. We will test the
hypothesis that the metabolic activity of each ganglion cell and its neighbors influences these signaling
mechanisms via oxidant production. In Specific Aim 3, we will examine the net influence of metabolic
modulation caused by light intensity changes (contrast adaptation) on ganglion cell output. We will test how
the actions of oxidants on specific features of the ganglion cell responses reflect the cell's metabolic state, and
how they adjust retinal output in normal and pathophysiological conditions.
These proposed studies will further our understanding of the cellular mechanisms that underlie ganglion cell
responses and retinal output. Our objectives are consistent with the health-related goals of the National Eye
Institute for understanding neuroprotective mechanisms in retinal neurons to prevent neurodegeneration,
including that induced by excessive levels of metabolic byproducts, as well as understanding the origin of
dysfunctional retinal signals that are detected with clinical tools essential for diagnosing and assessing the
progression of retinal disease.

## Key facts

- **NIH application ID:** 10892035
- **Project number:** 5R01EY033905-02
- **Recipient organization:** DOHENY EYE INSTITUTE
- **Principal Investigator:** Steven Andrew Barnes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892035

## Citation

> US National Institutes of Health, RePORTER application 10892035, Retinal Ganglion Cell Signaling Regulated By Intrinsic Reactive Oxygen Species (5R01EY033905-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892035. Licensed CC0.

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