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MMP-9 based immune-driven mechanisms of neovascular AMD

Award Number: R01EY035435
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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MMP-9 based immune-driven mechanisms of neovascular AMD - PROJECT SUMMARY/ABSTRACT The neovascular ‘wet’ form of age-related macular degeneration (nvAMD), whereby new blood vessels grow under the retina, requires treatment with anti-vascular endothelial growth factor eye injections typically every 1- 3 months for the remainder of patients’ lives due to persistent fluid, which can be visualized and quantified by optical coherence tomography (OCT) imaging. Recent research has implicated matrix metalloproteinase 9 (MMP9), expressed in immune cells of the retinal blood supply (termed choroid), as a mediator in the formation and persistence of nvAMD. This proposal will elucidate our understanding of this novel immune-based mechanism. Characteristics of patients with high-risk genotype of MMP9 will also be assessed, as they are associated with incomplete response to standard therapies for nvAMD. We will identify genetic regulatory regions that control expression of MMP9 and determine the immunologic activation profiles in patients with nvAMD. We will use artificial intelligence (AI)-based approaches to associate phenotypic features observable on OCT and OCT-angiography with high- and low-risk MMP9 genotypes in patients with nvAMD. Our outstanding team of interdisciplinary researchers will collaborate to employ state-of-the-art genomic and immunologic techniques to study the mechanisms of how MMP9 is implicated in nvAMD and fibrosis. Genetics will aid AI- and machine learning-based analysis of OCT images to learn new features associated with the most challenging patients afflicted with nvAMD. Unraveling the disease mechanisms associated with MMP9 will reveal new targets for therapeutic intervention. This proposal encompasses 5 of the 7 cross-cutting areas of emphasis the NEI laid out in the 5-year Strategic Plan on November 1, 2021. This is the next, necessary milestone in nvAMD that will help to address this major socioeconomic health burden.


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 = $540,439 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	3	1/21/2025	NON-COMPETING CONTINUATION	$540,439
														Subtotal = $540,439

Issue Date FY: 2024 ( Subtotal = $540,439 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	2	2/21/2024	NON-COMPETING CONTINUATION	$540,439
														Subtotal = $540,439

Issue Date FY: 2023 ( Subtotal = $540,439 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Vision Research	000	1	8/24/2023	NEW	$540,439
														Subtotal = $540,439

Grand Total All Awards = $1,621,317

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MMP-9 based immune-driven mechanisms of neovascular AMD

Award Number: R01EY035435

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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