# Mitochondrial reactive oxygen species act as autocrine neuromodulators in retinal ganglion cells

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $68,562

## Abstract

Project Summary/Abstract
Neurons continuously maintain ion gradients across their cell membrane in order to facilitate electrical signaling.
ATP produced by the mitochondria is required to re-establish these gradients following the electrical activity
necessary for information transmission. Reactive oxygen species (ROS) are produced as an inevitable
consequence of energy production in the mitochondria. ROS interact with many of the ion channels that control
neuronal excitability however the degree to which ROS modulate neuronal function under normal circumstances
is not clear. While a basal level of ROS is a normal feature of the intracellular milieu, prolonged elevation of ROS
is part of the metabolic dysregulation that appears to be a key factor in optic neuropathies, including glaucoma.
In retinal ganglion cells (RGCs) the rate of action potentials (spikes) produced by a visual scene is strongly
dependent on contrast, the range of light intensities varying around the mean. The retina adapts both to mean
luminance and contrast and reduces sensitivity in response to prolonged high contrast stimuli. The switch
between low and high contrast dramatically increases mean spike rate and consequently metabolic demand.
The primary focus of this research project is to understand how changes in ROS modulate the function of
genetically identified RGCs under normal conditions particularly during the shifts in metabolic demand that occur
during shifts in contrast.
Experiments proposed in Aim 1 will elaborate on preliminary data showing subtype specific modulation of RGC
excitability by elevating or reducing endogenous ROS levels. Experiments will test effects of elevated ROS levels
on excitatory and inhibitory input as well as intrinsic excitability using injected current steps. In Aim 2, I will used
paired, injected current steps as well as Gaussian white noise current injection of either low or high variance to
model states of low or high metabolic demand and determine the contribution of ROS to contrast adaptation.
Finally in Aim 3, I will investigate the underlying biophysics of the interaction of ROS with voltage-gated
conductances measured in nucleated patch recordings from identified RGC subtypes.
Metabolism, adaptation, and resilience to degeneration are fundamental features of neural function therefore
these studies will further our understanding of processes mediating visual function in the retina. This objective is
consistent with the health-related goals of the National Eye Institute for the understanding of retinal circuits and
the development of therapeutic approaches essential for the treatment and prevention of retinal disease.

## Key facts

- **NIH application ID:** 10157645
- **Project number:** 1F32EY032401-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Benjamin Smith
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157645

## Citation

> US National Institutes of Health, RePORTER application 10157645, Mitochondrial reactive oxygen species act as autocrine neuromodulators in retinal ganglion cells (1F32EY032401-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10157645. Licensed CC0.

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