# Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2024 · $617,323

## Abstract

Project Summary
The accumulation of mutant myocillin leads to decreased aqueous humor outflow and results in ER
dysfunction. Grp94 is a major chaperone localized to the ER that is responsible for modulating ER stress and
the folding of select client proteins to maintain proteostasis. Through a number of key studies, it has been
shown that Grp94 attempts to fold mutant myocillin, but instead co-aggregates and creates a toxic gain of
function for Grp94 that results in POAG. Recently, we discovered Grp94 selective inhibitors and demonstrated
both in vitro and in vivo that they reduced aggregation and restore intraocular pressure, providing a new
mechanism for the treatment of POAG. Therefore, we propose in this application to optimize our lead
compounds, determine their mechanism of action, and provide additional data to support their development as
topically administered therapeutics not only for POAG, but also steroid-induced glaucoma.

## Key facts

- **NIH application ID:** 10859324
- **Project number:** 1R01EY036107-01
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Brian S J Blagg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $617,323
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859324

## Citation

> US National Institutes of Health, RePORTER application 10859324, Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma (1R01EY036107-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10859324. Licensed CC0.

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