# The Aqueous Humor Outflow Resistance

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $373,450

## Abstract

Project Summary
Glaucoma is a major cause of blindness affecting over 67 million persons worldwide. Elevated intraocular
pressure (IOP) is the primary risk factor for glaucoma and reducing IOP is the only current effective treatment
for all forms of glaucoma. Cells within the juxtacanalicular region (JCT) of the trabecular meshwork (TM)
probably working in conjunction with Schlemm's canal inner wall endothelium (SCE) are responsible for a
robust IOP homeostasis mechanism in which the resistance to aqueous humor outflow is normally adjusted in
response to pressure disbalances. A key component of glaucoma is the loss of this IOP homeostatic capability.
This aqueous humor outflow resistance has long been recognized as a primary factor in glaucoma
development and has been studied extensively for over 65 years resulting in a large number of diverse
regulatory and modulatory processes to change it, including some recent therapeutic agents. Surprisingly,
neither the exact location nor molecular composition of this resistance is known in normal or in glaucomatous
eyes. Not surprisingly, it is very difficult to develop effective therapeutic resolutions to outflow resistance
dysfunction, when we do not even know what or where it is.
This application is narrowly focused on identifying and localizing the outflow resistance in normal and in
glaucomatous eyes.
Experimental and conceptual studies by us and many others support our working hypothesis that this
resistance resides primarily within the 2 m SC basement membrane with a small direct contribution by the SC
endothelial cells themselves. The glaucomatous resistance increase may reside in the same area and involve
the same molecules, or it may not.
We propose a set of direct studies that will localize this resistance and manipulations that will identify the
molecules involved. Studies will be conducted primarily in perfused human anterior segment organ culture and
in the new perfused anterior segment wedge culture system we have recently developed. Identifying and
localizing this outflow resistance will facilitate new more effective therapies for glaucomatous IOP elevation and
the loss of IOP homeostatic capability.

## Key facts

- **NIH application ID:** 10146404
- **Project number:** 5R01EY030238-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** TED S ACOTT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,450
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146404

## Citation

> US National Institutes of Health, RePORTER application 10146404, The Aqueous Humor Outflow Resistance (5R01EY030238-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146404. Licensed CC0.

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