# Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma

> **NIH NIH R01** · UNIVERSITY OF MISSOURI KANSAS CITY · 2021 · $375,875

## Abstract

Project Summary/Abstract
The proposal is in response to NEI's strategic plan, described recently by NEI in “Vision Research:
Needs, Gaps, and Opportunities”, and focuses on our most recent discoveries of a novel neuronal
mechanism rooted at the intersection of aging and the biological mechanisms of eye disease identified
as a high programmatic priority. The proposed research targets a novel mechanism of neuroprotection
utilizing intracellular calcium channels as drug targets to treat neurodegeneration in glaucoma.
Specifically, we plan to determine mechanisms of action and to measure preservation of neuronal
viability and function in model systems of glaucoma. The proposed research will allow us to generate
preclinical data needed for the development of novel neuroprotectants to complement existing therapies
targeting intraocular pressure: The intracellular free Ca2+ concentration of retinal ganglion cells like in
other neurons of the CNS is highly regulated and subject to dysregulation during aging. For the
development of acute and chronic degenerative diseases including glaucoma reducing the viability and
function of retinal ganglion cells (RGCs) several studies indicate that both changes in intracellular second
messenger concentration and pathological increases in the intracellular Ca2+ concentration promote
pathogenesis. The present application will test the hypothesis that Ca2+ signaling of RGCs is functionally
regulated by an immediate early gene product upregulated in RGCs after a neurodegenerative insult to
generate a cellular defense mechanism. This hypothesis is based on strong preliminary evidence that
normal aging of the retina is mechanistically similar to glaucoma disease processes and can be exploited
to devise novel treatments for glaucoma. The proposed experiments designed to test this hypothesis will
investigate the molecular, cellular and functional mechanisms underlying this interaction under
experimentally induced disease conditions in models of glaucoma. The overall goal of the proposed
study is to identify a novel mechanism of RGC neuroprotection and determine its potential as a strategy
for neuroprotective therapies targeting RGCs. This therapy approach will have the potential to be both
preventative and therapeutic in nature and to complement existing treatment designs and rationales.

## Key facts

- **NIH application ID:** 10087941
- **Project number:** 5R01EY031248-02
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **Principal Investigator:** Peter Koulen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,875
- **Award type:** 5
- **Project period:** 2020-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087941

## Citation

> US National Institutes of Health, RePORTER application 10087941, Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma (5R01EY031248-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10087941. Licensed CC0.

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