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Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye

Award Number: R01EY030501
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye - Project Summary Glaucoma is a leading cause of permanent vision loss worldwide, and the only treatment is to lower intraocular pressure (IOP). IOP is governed by how aqueous humor (the fluid in the eye) exits the drainage pathways that start at the trabecular meshwork (TM) before moving into Schlemm’s canal, collector channels, an intrascleral venous plexus, and aqueous/episcleral veins. However, recent discoveries have demonstrated that aqueous humor outflow (AHO) is not static and unchanging but is more complex than a simple linear depiction. AHO shows dynamic variable behavior (or dynamic variable outflow; DVO) where it is variable with segmental regions of the eye displaying high- or low-AHO, is dynamic where AHO can spontaneously increase or decrease in different locations of the eye, and is improvable where drugs or surgeries can enhance it. Thus, this proposal aims to better study DVO by uncovering how and why AHO can be improved in certain regions of the eye. This helps understand what may have been lost in disease and what may be targeted in IOP-lowering treatments. The central hypothesis in this proposal is that glaucoma therapies work at improvable DVO regions and that by facilitating DVO research and knowing where and how this occurs, personalized glaucoma treatments can be crafted for individual patients. To accomplish this, we will utilize cutting edge structural imaging tools such as anterior segment optical coherence tomography (OCT). We will also use a method called aqueous angiography that we developed on a previous National Institutes of Health and National Eye Institute grant. Aqueous angiography allows researchers to see exactly where aqueous humor is flowing in the eye in a real-time fashion. With these tools, we will study ex vivo human eyes in the laboratory and in donor in vivo eyes to yield the most germane discoveries for glaucoma and glaucoma treatment. In Specific Aim (SA1), we will discover how DVO is regulated by studying the structural and molecular basis of segmental and dynamic AHO using imaging and screen-based tools on human donor and ex vivo eyes in the laboratory. In SA2, we will use ex vivo human eyes to study how glaucoma surgeries in different locations in the eye impact IOP lowering and what hurdles the proximal vs. distal AHO pathways present to surgical success. In SA3, we will investigate how glaucoma pharmacological drugs (currently FDA-approved drug formulations and delivery) alter DVO in ex vivo and donor eyes, specifically looking at the parts of the eye that are improved by treatment to understand why these areas had the capacity to do so. Through the results of this proposal, we will better understand the dynamic processes of how intraocular fluid leaves the eye as a way to enhance current glaucoma treatments and to create a springboard to innovate new ones.


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: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	6	5/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $424,981 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	6	6/17/2024	NON-COMPETING CONTINUATION	$424,981
														Subtotal = $424,981

Issue Date FY: 2023 ( Subtotal = $445,792 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	5	6/15/2023	NON-COMPETING CONTINUATION	$445,792
														Subtotal = $445,792

Issue Date FY: 2022 ( Subtotal = $417,355 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	002	4	5/4/2022	NON-COMPETING CONTINUATION	$417,355
2022	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	001	3	3/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$269,074
2022	2021	DOHENY EYE INSTITUTE	150 N ORANGE GROVE BLVD	PASADENA	CA	91103	LOS ANGELES	USA	Vision Research	004	2	8/18/2022	NON-COMPETING CONTINUATION	-$148,054
2022	2021	DOHENY EYE INSTITUTE	150 N ORANGE GROVE BLVD	PASADENA	CA	91103	LOS ANGELES	USA	Vision Research	000	2	3/21/2022	NON-COMPETING CONTINUATION	-$269,074
2022	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	005	3	8/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$206,825
2022	2020	DOHENY EYE INSTITUTE	150 N ORANGE GROVE BLVD	PASADENA	CA	91103	LOS ANGELES	USA	Vision Research	003	1	8/18/2022	NEW	-$58,771
														Subtotal = $417,355

Issue Date FY: 2021 ( Subtotal = $417,128 )
2021	2021	DOHENY EYE INSTITUTE	1355 SAN PABLO ST	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	000	2	5/13/2021	NON-COMPETING CONTINUATION	$417,128
														Subtotal = $417,128

Issue Date FY: 2020 ( Subtotal = $451,484 )
2020	2020	DOHENY EYE INSTITUTE	1355 SAN PABLO ST	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	000	1	5/1/2020	NEW	$451,484
														Subtotal = $451,484

Grand Total All Awards = $2,156,740

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Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye

Award Number: R01EY030501

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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