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The Aqueous Humor Outflow Resistance

Award Number: R01EY030238
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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The Aqueous Humor Outflow Resistance - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	5	11/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $407,718 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	6	7/29/2025	COMPETING CONTINUATION	$407,718
														Subtotal = $407,718

Issue Date FY: 2023 ( Subtotal = $385,000 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	5	5/15/2023	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2022 ( Subtotal = $373,450 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	4	4/18/2022	NON-COMPETING CONTINUATION	$373,450
														Subtotal = $373,450

Issue Date FY: 2021 ( Subtotal = $373,450 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	3	4/29/2021	NON-COMPETING CONTINUATION	$373,450
														Subtotal = $373,450

Issue Date FY: 2020 ( Subtotal = $385,000 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	2	4/16/2020	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2019 ( Subtotal = $385,000 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Vision Research	000	1	4/22/2019	NEW	$385,000
														Subtotal = $385,000

Grand Total All Awards = $2,309,618

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The Aqueous Humor Outflow Resistance

Award Number: R01EY030238

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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