# TM/SC-interface-on-a-chip for mechanistic studies of outflow regulation.

> **NIH NIH R21** · UPSTATE MEDICAL UNIVERSITY · 2024 · $244,015

## Abstract

PROJECT SUMMARY/ABSTRACT
The trabecular meshwork (TM)/Schlemm’s canal (SC)-interface is critical for normal aqueous humor outflow
function and intraocular pressure. Flow across the circumference of the outflow tract is non-uniform or
segmental, with low-flow (LF) regions exhibiting higher extracellular matrix stiffness than high-flow (HF)
regions. Dysfunction of the outflow tract causes decreased aqueous drainage and consequently increased
intraocular pressure that poses a serious threat to normal vision. However, despite the strong association of
outflow impairment with development of high-pressure glaucoma, the underlying mechanisms – including
contributions from LF/HF regions – are incompletely understood. This largely stems from the inability of current
outflow tissue models to precisely simulate the dynamic TM/SC-interface at high resolution necessary for in-
depth mechanistic studies. To overcome critical limitations of previous outflow tissue replicas, this work seeks
to generate a first-in-class TM/SC-interface-on-a-chip that accurately recapitulates the outflow tissue’s complex
microenvironment and segmental elasticity profile. The novel 3D outflow tissue platform allows us to dissect
the mechanisms of resistance generation by selectively manipulating individual outflow pathway components in
ways otherwise not possible using other models. This will enable quantitative measurements of dynamic
changes at the interface in real-time, while also being compatible with critical end-point tests. Based on key
preliminary data acquired by our investigative team, we propose the following specific aims:
Aim 1: Design and validate a microfluidic chip-based TM/SC-interface to investigate dynamic outflow
regulation.
Aim 2: Investigate segmental outflow regulation using localized ECM stiffness patterns containing region-
specific TM cells.

## Key facts

- **NIH application ID:** 10869467
- **Project number:** 1R21EY036189-01
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Samuel Herberg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $244,015
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869467

## Citation

> US National Institutes of Health, RePORTER application 10869467, TM/SC-interface-on-a-chip for mechanistic studies of outflow regulation. (1R21EY036189-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869467. Licensed CC0.

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