# Role of gasderminD in ganglion cell dysfunction and injury

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $186,118

## Abstract

In primary glaucoma, ocular hypertension (OHT) stress triggers a neurotoxic cascade leading to selective
death of retinal ganglion cells (RGC). However, the molecular mechanism transforming mechanical, non-ischemic stress into RGC dysfunction, injury and death in glaucoma remains highly debated. We discovered
that OHT stress of various intensity and duration acutely activates neuronal NLRP1/NLRP3 inflammasomes
that release of interleukin-1β cytokine and trigger GasderminD pore formation in RGCs in vivo.
This project is premised on our exciting preliminary data where inflammasome blockade suppressed GsdmD
activation and prevented dysfunction and loss of OHT-challenged RGCs in both acute OHT and chronic OHT
(glaucoma) models. We designed this project to test our new hypothesis that metabolic and physiological
dysfunction of RGCs leading to their loss in OHT injury is facilitated by activation of GsdmD pores in
mitochondria and plasma membranes. If our hypothesis is correct, modulation of inflammasome pathway in the
retina would prevent functional decline and loss of RGC in glaucoma.

## Key facts

- **NIH application ID:** 10326850
- **Project number:** 5R21EY032261-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** VALERY I SHESTOPALOV
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $186,118
- **Award type:** 5
- **Project period:** 2021-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326850

## Citation

> US National Institutes of Health, RePORTER application 10326850, Role of gasderminD in ganglion cell dysfunction and injury (5R21EY032261-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10326850. Licensed CC0.

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