# Schlemm’s canal on a chip: A platform for screening a novel class of glaucoma medications

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $193,467

## Abstract

Glaucoma is a major cause of blindness. A major risk factor for glaucoma, and the only treatable risk factor, is
elevated intraocular pressure (IOP). IOP is largely determined by the function of the tissues of the conventional
outflow pathway, specifically the trabecular meshwork and the inner wall of Schlemm's canal (SC), and increased
fluid flow resistance in these tissues causes elevated IOP. The inner wall of SC has been largely ignored as a
target for IOP-lowering therapies, in part because our understanding of this tissue's function has been poor.
However, recent research findings have greatly improved our understanding and motivate this proposal.
The goal of this R21 is to optimize, characterize and validate a rapid and accurate assay system that interrogates
the fluid conductivity of cultured SC cells, motivated by the knowledge that increasing SC cellular conductivity
will lower IOP. The long-term vision is to use this assay system to serve as a pre-clinical screening tool for drug
discovery and thereby accelerate discovery of a novel class of “SC-active” compounds for treating ocular
hypertension in glaucoma patients. We expect such SC-active compounds to have fewer side effects compared
to other IOP-lowering compounds, including avoidance of conjunctival hyperemia.
Because the hydraulic conductivity of SC cells is normally controlled by the formation of membrane-delimited
fluid pathways (“pores”), the assay system specifically focuses on detection of such pores in a high-content
manner. More particularly, the focus is on intracellular pores (I pores), thought to form an under-exploited
secondary aqueous outflow pathway. The key elements of this assay system include: (1) primary SC cell isolation
from non-glaucomatous and glaucomatous human eyes; (2) substrate micropatterning to control cultured cell
spread/height and enhance assay rigor; (3) delivery of focal mechanical stretch to the apical surface of cultured
SC cells using superparamagnetic microspheres and external magnets; (4) a novel fluorescent assay that,
together with automated light microscopy and image processing tools, allows the rapid detection of pores that
form in SC cells in a manner that minimizes introduction of inadvertent bias; and (5) a high-content format in
which cells are cultured in 96 well plates, allowing relatively rapid testing of the effects of agents on SC cells.
There is a high degree of rigor in the proposal, which is underpinned by a significant body of peer-reviewed
research and strong preliminary data. The applicants have extensive experience in culturing and characterizing
human primary SC cells, and the proposal includes a variety of positive and negative controls to validate the
assay system. Further, the multi-well assay format has the advantage of naturally allowing multiple technical and
biological replicates on each 96 well plate, enabling characterization of repeatability and good statistical rigor.
It is expected, as suggested by the proposa...

## Key facts

- **NIH application ID:** 10293948
- **Project number:** 1R21EY033142-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** C ROSS ETHIER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,467
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293948

## Citation

> US National Institutes of Health, RePORTER application 10293948, Schlemm’s canal on a chip: A platform for screening a novel class of glaucoma medications (1R21EY033142-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10293948. Licensed CC0.

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