Thursday, January 1, 2026 1/1/2026

Ref-1 in Retinal Neovascularization

Award Number: F31EY035171
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/14/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Ref-1 in Retinal Neovascularization - PROJECT SUMMARY Retinal neovascularization impairs visual function and is a hallmark of several neovascular eye diseases, including retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Diabetic retinopathy (DR) is the leading cause of vision-loss in working age adults, and ROP is the leading cause of preventable blindness in children. Current treatments include intravitreal (IVT) injections of anti-vascular endothelial growth factor (VEGF) biologics. However, these therapeutics are often accompanied by high treatment burden and resistance to therapy. Previous research indicates that VEGF alone is not sufficient for induction of neovascularization, suggesting that multiple disease-relevant pathways may be targeted to increase therapeutic response. Thus, there is a critical need to develop novel therapies that modulate multiple disease- relevant pathways and circumvent the issues with IVT injections. Prior studies indicate that APE1/Ref-1, a multifunctional protein with both endonuclease (APE1) and redox activity (Ref-1), regulates multiple transcription factors that are linked to retinal neovascularization. Preliminary data in the laser-induced choroidal neovascularization model demonstrated upregulation of Ref-1 during neovascularization, and oral administration of a small molecule Ref-1 redox inhibitor decreased disease severity. RNA-seq of human retinal endothelial cells revealed that a Ref-1 redox inhibitor downregulated Wnt signaling genes, implying that Ref-1 redox function modulates neovascularization through the Wnt signaling. But, the underlying molecular mechanisms of the novel Ref-1 target in retinal neovascularization have yet to be elucidated. Identifying the molecular mechanism underlying Ref-1 in retinal neovascularization is critical in developing novel therapies to reduce vision loss. The hypothesis of this proposal is that Ref-1 redox activity promotes induction of retinal neovascularization via activation of the Wnt signaling pathway, and reducing Ref-1 redox activity with a novel Ref-1 redox inhibitor will exhibit potent therapeutic effects via inhibition of the Wnt signaling pathway. Aim 1 will analyze the spatiotemporal expression of Ref-1 in retinal neovascularization in the oxygen-induced retinopathy (OIR) mouse model, the Vldlr-/- mouse model, and in human PDR tissue. Aim 2 will analyze the mechanism of Ref-1 regulation of the Wnt pathway in retinal endothelial cells through functional in vitro assays. Aim 3 will assess anti-angiogenic effects of a Ref-1 inhibitor in vivo by administering oral Ref-1 inhibitor in the OIR mouse model and evaluating changes in neovascularization. Effects on the Wnt signaling pathway will also be assessed using immunofluorescence. Completion of this study will bolster understanding of Ref-1 in neovascular eye diseases and provide a novel therapeutic strategy to combat vision loss and blindness due to these diseases.


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 = -$1,401 )
2026	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	2	12/19/2025	NON-COMPETING CONTINUATION	-$1,401
														Subtotal = -$1,401

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	001	3	9/9/2025	NON-COMPETING CONTINUATION	-$33,538
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	3	6/10/2025	NON-COMPETING CONTINUATION	$33,538
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $33,244 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	2	6/14/2024	NON-COMPETING CONTINUATION	$33,244
														Subtotal = $33,244

Issue Date FY: 2023 ( Subtotal = $36,044 )
2023	2023	REDACTED DUE TO PII		INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	001	1	6/14/2023	NEW	$0
2023	2023	REDACTED DUE TO PII		INDIANAPOLIS	IN	46202	MARION	USA	Vision Research	000	1	6/14/2023	NEW	$36,044
														Subtotal = $36,044

Grand Total All Awards = $67,887

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Ref-1 in Retinal Neovascularization

Award Number: F31EY035171

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/14/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer