# Purines and the health of retinal ganglion cells

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $479,727

## Abstract

Project Summary
Glaucoma is a major cause of blindness, characterized by the death of retinal ganglion cells
(RGCs) and loss of vision. An elevated intraocular pressure (IOP) is the biggest risk factor in the
disease, but localized inflammatory signaling can also contribute to the pathology. This proposal
will investigate the pathways linking elevated IOP to local inflammatory signaling and RGC
death, based on the innovative hypothesis that ATP-dependent release of the inflammatory
cytokine ͎IL-1β from microglial cells links mechanical strain to vision loss in glaucoma. Stretch-
dependent ATP release from optic nerve head astrocytes will be compared using astrocytes
missing genes implicated in mechanosensitive ATP release. The most promising candidates will
be examined in vivo using a mouse model for chronic ocular hypertension; reduced levels of
inflammatory responses or RGC death will implicate mechanosensitive ATP release. The ability
of ATP to enhance microglial migration and IL-1β release will be explored in isolated retinal
microglial cells to enable detailed characterization. The contribution to RGCs death in a model
of chronic ocular hypertension will be confirmed. The ability of IL-1β to kill RGCs in vivo will be
confirmed and its contribution to death in ocular hypertension tested. The effect of substrate
stiffness on the magnitude of mechanosensitive ATP release will be investigated in vitro and in
vivo. Finally, the links between ATP release and IL-1β will be confirmed in the retina of
glaucomatous humans. In summary, this proposal will connect elevated IOP with
proinflammatory responses through aberrant purinergic signaling. This novel hypothesis will
advance our understanding of glaucoma while identifying possible new targets for intervention.

## Key facts

- **NIH application ID:** 9876947
- **Project number:** 5R01EY015537-13
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** CLAIRE H MITCHELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $479,727
- **Award type:** 5
- **Project period:** 2005-06-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876947

## Citation

> US National Institutes of Health, RePORTER application 9876947, Purines and the health of retinal ganglion cells (5R01EY015537-13). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9876947. Licensed CC0.

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