Wednesday, December 31, 2025 12/31/2025

Role of Macrophages in ocular GVHD

Award Number: R01EY034672
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

Group Awards By:

View Award Description

Role of Macrophages in ocular GVHD - Project Summary/Abstract Graft versus host disease (GVHD) is an immune-mediated condition affecting many organs. It is categorized into acute and chronic subtypes. Eyes are affected in 60-90% of the patients with chronic GVHD resulting in significant visual morbidity. About half of the ocular GVHD (oGVHD) patients develop steroid- refractory conjunctival and lacrimal fibrosis and severe dry eye, sometimes with ocular perforation and loss of globe. Pathophysiology of oGVHD remains incompletely understood. The current proposal will investigate the role of host and donor macrophages, their phenotypic changes, and their crosstalk with fibroblasts and goblet cells as mechanisms underlying oGVHD-associated ocular surface damage, fibrosis, and dry eye. The long- term goal is to understand the immune-mediated pathophysiological basis of oGVHD for its prevention and better therapeutic management. This proposal will use two mouse models of allogeneic bone marrow transplantation to induce oGVHD. These models recapitulate many features of GVHD-associated ocular surface damage, including a decrease in tear volume, signs of corneal keratopathy, conjunctival fibrosis, and loss of goblet cells. Aim 1 will investigate whether irradiation, host macrophage activation, and the influx of donor marrow-derived macrophages initiate and perpetuate ocular surface injury in oGVHD. Aim 2 will identify whether profibrotic mediators released by macrophages cause transdifferentiation of conjunctival and lacrimal gland fibroblasts to elicit oGVHD-associated fibrosis. Aim 2 will also test the role of the fibroblast-mediated release of macrophage colony-stimulating factor-1 (CSF-1) and other chemokines in recruiting donor macrophages to the ocular surface. Furthermore, aim 2 will evaluate whether pexidartinib, a CSF-1 receptor inhibitor, can attenuate oGVHD by depleting conjunctival and lacrimal gland macrophages. Aim 3 will investigate whether rescue of goblet cell loss by IL-13 can mitigate oGVHD-associated dry eye. Aim 3 will also identify the macrophage receptors involved in mediating the biological effects of goblet cell mucins. The results of this study will provide data on the role of host-donor macrophages, their interaction with fibroblasts and goblet cells as underlying mechanisms in oGVHD pathology and will potentially identify novel therapeutic approaches for the management of oGVHD.


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 = $342,000 )
2026	2026	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Vision Research	000	4	12/4/2025	NON-COMPETING CONTINUATION	$342,000
														Subtotal = $342,000

Issue Date FY: 2025 ( Subtotal = $342,000 )
2025	2025	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Vision Research	000	3	12/4/2024	NON-COMPETING CONTINUATION	$342,000
														Subtotal = $342,000

Issue Date FY: 2024 ( Subtotal = $342,000 )
2024	2024	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Vision Research	000	2	12/11/2023	NON-COMPETING CONTINUATION	$342,000
														Subtotal = $342,000

Issue Date FY: 2023 ( Subtotal = $342,000 )
2023	2023	CHAPMAN UNIVERSITY	1 UNIVERSITY DR	ORANGE	CA	92866	ORANGE	USA	Vision Research	000	1	1/27/2023	NEW	$342,000
														Subtotal = $342,000

Grand Total All Awards = $1,368,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of Macrophages in ocular GVHD

Award Number: R01EY034672

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer