# Role of cellular memory in glaucoma.

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2022 · $407,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Fibrotic-like dysfunction and extracellular matrix stiffening of the trabecular meshwork (TM) is a hallmark of
persistent intraocular pressure elevation in primary open-angle glaucoma. Short-term exposure of healthy TM
cells to mechanical insult induces characteristic glaucoma-like pathology, which is recoverable after cessation
of insult. In contrast, glaucomatous TM cells retain a pathologic phenotype via a stored mechanical memory
despite culture within a soft tissue-like matrix environment. The overall objective of this proposal is to identify
how mechanical memory in TM cells is first formed and then stored, and how it contributes to the persistence
of glaucomatous cellular dysfunction. We hypothesize that TM cell mechanical memory plays a central role in
persistent tissue failure in glaucoma. In Aim 1, we will fully characterize TM cell mechanical memory. Cells
“sense” their mechanical environment through mechanotransduction. In Aim 2, we will investigate the role of a
key mechanoregulatory transcriptional co-activator Yes-associated protein (YAP) in modulating TM cell
mechanical memory. Cells “store” mechanical memory through chromatin remodeling and epigenetic
modifications. In Aim 3, we will investigate the role of epigenetic modifications in long-term TM cell mechanical
memory retention. We will use our innovative bioengineered primary human TM cell-encapsulated hydrogel
and dynamically tune matrix stiffness to test our hypothesis. Our specific aims are:
Aim 1: To determine how mechanical memory persistence contributes to glaucomatous TM cell dysfunction.
Aim 2: To determine how YAP mechanotransduction contributes to TM cell mechanical memory acquisition
and retention.
Aim 3: To determine how epigenetic modifications contribute to long-term TM cell mechanical memory
retention.

## Key facts

- **NIH application ID:** 10501318
- **Project number:** 1R01EY034096-01
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Samuel Herberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $407,500
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501318

## Citation

> US National Institutes of Health, RePORTER application 10501318, Role of cellular memory in glaucoma. (1R01EY034096-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10501318. Licensed CC0.

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