Sunday, August 17, 2025 8/17/2025

Characterization of the role of MIF on retinal health and disease

Award Number: R01EY032573
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

Group Awards By:

View Award Description

Characterization of the role of MIF on retinal health and disease - Abstract This research focuses on filling gaps in knowledge about the precise molecular pathways that underpin retinal inflammation and impact crosstalk from ischemic retinal diseases, including diabetic retinopathy, vascular diseases, retinopathy of prematurity, and sickle cell retinopathy. Current treatments are often inadequate to prevent vision loss, and adding selective targeting of additional inflammatory mediators may offer new vision-saving therapies. We have identified that (1) the pro- inflammatory cytokine macrophage migration inhibitor factor (MIF) is a druggable target for preventing retinal gliosis and photoreceptor loss in retinal detachment. (2) MIF is up-regulated in the N-methyl-D- aspartic acid (NMDA) damage model which simulates ischemia-mediated retinal excitotoxicity; pharmacologic and genetic inhibition of MIF increases neuronal survival in this model. (3) Clinically we identified a genetic association of MIF promoter polymorphisms with epiretinal membrane formation. Müller glia/astrocytes (MG) are the predominant components of ERM suggesting that MIF could play an important role in the pathological function of retinal glia. MIF inhibitors are in clinical evaluation for a variety of systemic diseases. While inhibition of MIF’s pro-inflammatory effects may indeed underlie the enhanced neuronal survival from MIF d-DT inhibitors, our recent findings strongly suggest that alternative mechanisms also exist. MIF is highly expressed in the Müller glia/astrocytes and it has been hypothesized to be a glial growth factor. Our preliminary data show that conditional inhibition of MIF in the MG enhances the survival of retinal neurons during damage and affects the MG JAK/STAT pathway. Herein, Specific Aim 1 will test the hypothesis that MIF inhibition promotes neuronal survival in retinal damage by activating the gp130/JAK/STAT signaling pathway of Müller glia/astrocytes. In chick and murine NMDA models, we will use pharmacologic and genetic approaches to assess the impact on MG signaling pathways and neuronal survival induced by MIF inhibition. Specific Aim 2 will test the hypothesis that conditional deletion of Müller glia/astrocyte MIF up-regulates the gp130/JAK/STAT pathway and enhances the survival of retinal neurons. In Specific Aim 3 we will develop a single cell RNA-seq database of damaged and undamaged retina treated with MIF inhibitors and/or MG-specific genetic deletion of MIF. We will comprehensively evaluate the transcriptional changes at single-cell resolution in the glia and retinal neurons that result from inhibition of MIF. This research will define the important functional relationships between MIF and signaling pathways on specific cells during retinal damage. The fundamental knowledge gained from understanding the transcriptome ‘switch’ will set the stage for future studies targeting key molecular pathways that are druggable with minimal side effects, but able to prevent and recover visual loss from retinal damage.


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 = $393,750 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	5	8/4/2025	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2024 ( Subtotal = $499,988 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	001	4	8/12/2024	SUPPLEMENT FOR EXPANSION	$106,238
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	4	7/31/2024	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $499,988

Issue Date FY: 2023 ( Subtotal = $393,750 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	3	7/13/2023	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2022 ( Subtotal = $381,938 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	2	7/28/2022	NON-COMPETING CONTINUATION	$381,938
														Subtotal = $381,938

Issue Date FY: 2021 ( Subtotal = $393,750 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	1	8/27/2021	NEW	$393,750
														Subtotal = $393,750

Grand Total All Awards = $2,063,176

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Characterization of the role of MIF on retinal health and disease

Award Number: R01EY032573

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer