Monday, June 30, 2025 6/30/2025

Investigating mechanisms of IL-27-induced photoreceptor protection and rescued vision

Award Number: R01EY036232
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2028

Group Awards By:

View Award Description

Investigating mechanisms of IL-27-induced photoreceptor protection and rescued vision - Dysregulated inflammation contributes to retinal degeneration. Although inflammatory cells may initially limit retinal damage by phagocytosing dying mutant photoreceptors and secreting reparative molecules, excessive inflammation causes recruitment of additional reactive microglia, phagocytosis of viable photoreceptors and toxic cytokine release, which accelerates retinal degeneration irrespective of the primary mutation. Therefore, a central challenge for developing anti-inflammatory therapies for retinal degenerations is to selectively suppress detrimental inflammation while maintaining beneficial inflammatory responses. We recently demonstrated that the cytokine IL-27 regulates beneficial and detrimental inflammatory signals in the retina and protects photoreceptors. IL-27 is a pleiotropic cytokine that regulates tissue reactions to infection, neuronal disease and tumors. We found that higher endogenous IL-27 levels were associated with photoreceptor protection induced by an innate immunity inhibitor in the rd10 mouse model of inherited retinal degeneration. In studies directly testing IL-27 function, we demonstrated that intravitreal injections of IL-27 into rd10 led to reduced pro-inflammatory cytokines, increased rod and cone photoreceptor survival and prolonged improvement in visual acuity. Additionally, IL-27 increased markers of protective microglia and reduced neurotoxic microglia. Because most research to date has focused on pro-inflammatory signals in the retina, a major unanswered question is how anti-inflammatory regulators such as IL-27 reduce neurotoxic inflammation during retinal degeneration. This proposed study will build upon our exciting data by defining mechanisms by which IL-27 signaling regulates inflammation and promotes photoreceptor survival (Aim 1). Additionally, IL-27 is expressed in Muller glia and IL-27 receptors are in microglia but whether these cells coordinate to regulate inflammation through IL-27 is not known. We will use conditional knockout mice and gene overexpression to identify whether a novel Muller glia and microglia cytokine-cytokine receptor signaling axis mediates IL-27-induced photoreceptor protection (Aim 2). The research team combines the expertise of the PI, Abigail Hackam – retinal degeneration and neuroinflammation, and collaborator Stefan Kurtenbach – scRNA seq and transcriptomics. The findings from this study will be significant to identifying a novel regulatory signal that controls inflammation, which will be relevant for precisely controlling inflammation and restoring tissue homeostasis during retinal degeneration. We will also generate novel insights into the roles of Muller glia-microglia interactions in controlling retinal inflammation. Finally, by characterizing a potential new therapeutic approach that is not dependent on the primary mutation, this study will set the foundation for developing IL-27 as a therapeutic strategy for protecting photoreceptors and rescuing vision during retinal disease.


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 = $431,317 )
2025	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Vision Research	000	2	4/10/2025	NON-COMPETING CONTINUATION	$431,317
														Subtotal = $431,317

Issue Date FY: 2024 ( Subtotal = $432,700 )
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Vision Research	000	1	4/10/2024	NEW	$432,700
														Subtotal = $432,700

Grand Total All Awards = $864,017

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating mechanisms of IL-27-induced photoreceptor protection and rescued vision

Award Number: R01EY036232

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer