# Astrocyte Networks as Therapeutic Targets in Glaucomatous Neurodegeneration

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2022 · $31,904

## Abstract

Project Summary/Abstract
Glaucoma, the leading cause of irreversible vision loss characterized by the degeneration of retinal ganglion
cells (RGCs) and their axons, will affect an estimated 100 million people worldwide by the year 2040.
Sensitivity to intraocular pressure (IOP) is the only modifiable risk factor in glaucoma. IOP can be reduced by a
number of hypotensive therapies, which often slow progression, but many patients continue to lose vision
despite significant pressure control. IOP-related stress is conveyed by mechanisms that pique RGC axons
within the optic nerve head. Thus, the first cellular responders to stress likely reside in the optic nerve head
and represent primary targets for neuroprotective treatment. In this region, axons are located in close proximity
to astrocytes. Astrocytes are intimately involved in the response to neurodegenerative stress and have become
an attractive target for the development of neuroprotective therapies. Astrocytes are densely interconnected by
gap junctions, primarily composed of the protein connexin-43 (Cx43), and can function as a broader network of
cells. Such networks are capable of enhancing astrocyte homeostatic capacities, including metabolite
distribution and extracellular ionic buffering, but their role in neurodegenerative disease is an emerging field.
Early glaucomatous degeneration is characterized in part by enhanced RGC excitability and a reduction in
axon function. Interestingly, a subset of RGCs which produce sustained responses at light offset (αOFF-S)
appear to be more vulnerable to IOP-related stress. Astrocytic networks play key roles at this early stage of
glaucoma. Work in the Calkins lab demonstrated that astrocyte-specific deletion of Cx43 grossly accelerates
degenerative changes in a mouse model of glaucoma. Preliminary experiments indicate that astrocytic Cx43
deletion preferentially alters the firing properties of αOFF-S RGCs. This proposal expands upon these findings,
aiming to illuminate the mechanisms underlying the differential susceptibility of RGC types and to explore the
importance of astrocyte networks in enhancing one neuroprotective function – buffering the contents of the
extracellular environment. Electrophysiologic, pharmacologic, and cell imaging techniques, alongside a mouse
model of glaucoma, will be employed to accomplish these aims. These studies will provide important insight
into the early physiologic events in glaucomatous neurodegeneration and establish a framework for future
neuroprotective therapies targeting astrocytes. The training plan outlined in this proposal is strengthened by an
abundance of resources and expertise, as well as strong mentorship and a commitment to training an
independent physician scientist.

## Key facts

- **NIH application ID:** 10532932
- **Project number:** 1F30EY033627-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Andrew M Boal
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,904
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532932

## Citation

> US National Institutes of Health, RePORTER application 10532932, Astrocyte Networks as Therapeutic Targets in Glaucomatous Neurodegeneration (1F30EY033627-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10532932. Licensed CC0.

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