# Retinal Neuronal Signaling in Early Diabetes

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2023 · $1

## Abstract

Project Summary
Diabetic retinopathy is a disease of both neurons and vasculature in the retina. Visual function deficits and
neuronal retinal dysfunction from electroretinograms, are some of the earliest identifiable diabetic retinal
problems, especially in the dim light activated rod pathways. Dysfunction of the inner retina - bipolar cells that
receive rod input, ganglion cells that receive bipolar cell input and amacrine cells that modulate this pathway-
is tied to the development of serious diabetic retinal problems. We have shown deficits in light-evoked
responses of rod pathway inner retinal neurons that are not due to cell death, but the neuronal mechanisms
that cause these deficits are unknown and the focus of this proposal. We will identify how a loss in dopamine
and Ca2+ signaling in the inner retina impacts light evoked vision loss, and we will modulate these pathways to
determine if they can be future targets for preventing diabetic retinal dysfunction and the neuronal progression
of vision loss. Dopamine is released by dopaminergic amacrine cells to allow retinal adaptation to increasing
background light levels and GABA release from other amacrine cells modulates the timing and spatial
sensitivity of ganglion cells, increasing the sensitivity of vision to small stimuli. Using a mouse model of STZ
induced diabetes we have shown that dopamine receptor sensitivity and light adaptation in one type of
ganglion cell and Ca2+ signaling in amacrine cells in the rod pathway are reduced, suggesting that ganglion cell
output to the brain is altered leading to diabetic visual deficits. We will use our expertise in analyzing retinal
signaling to determine the roles of dopamine and Ca2+ signaling changes in the diabetic retina using
physiological signaling, genetically modified mouse models and optogenetic stimulation. In Aim 1 we will
determine if the diabetes induced reduction in dopamine levels reduces dopamine receptor sensitivity of the
inner retina in the rod pathway, using single cell electrophysiology recordings of the responses of rod bipolar
cells and ganglion cells to light and immunohistochemical and in situ hybridization analysis. In Aim 2 we will
determine if the release and retinal function of dopamine in light adaptation are reduced in diabetes, using
recordings of physiological responses to increasing background light levels at the single cell level, in vitro ERGs
and direct dopamine release measurements. In Aim 3 we will determine what diabetes induced changes in
amacrine cell Ca2+ signaling cause reduced rod pathway inhibition by stimulating multiple amacrine cell inputs
to the rod pathway directly either electrically or optogenetically and blocking specific components of Ca2+
signaling. These proposed studies will significantly expand our understanding of the mechanisms and
progression of early diabetic retinal neuronal damage and are part of our long term goal to develop targets for
therapeutics to intervene at an early time ...

## Key facts

- **NIH application ID:** 10676970
- **Project number:** 5R01EY026027-08
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** ERIKA D. EGGERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2015-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10676970

## Citation

> US National Institutes of Health, RePORTER application 10676970, Retinal Neuronal Signaling in Early Diabetes (5R01EY026027-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10676970. Licensed CC0.

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