Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanistic investigations of tryptophan catabolites for vision improvement in Multiple Sclerosis

Award Number: R21EY037427
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

Group Awards By:

View Award Description

Mechanistic investigations of tryptophan catabolites for vision improvement in Multiple Sclerosis - Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation, demyelination and neurodegeneration within the central nervous system. Optic neuritis is the most prevalent ocular complication experienced by people with MS (pwMS), and repeated episodes can culminate in irreversible vision loss. Yet, effective treatments remain an important unmet need. Healthy diets have been linked to better outcomes for pwMS, but there is currently no consensus as to which dietary recommendations confer the most benefit. Using a rodent model of autoimmune-mediated demyelination called experimental autoimmune encephalomyelitis (EAE), we recently discovered that a therapeutic ketogenic diet (KD) restored visual function and optic nerve integrity when fed to symptomatic mice experiencing optic neuritis and vision loss. The goal of this application is to characterize metabolites and pathways that confer to the KD the capacity to restore vision and optic nerve integrity. RNA-seq analysis of optic nerves identified changes in gene expression coordinated by a nuclear receptor transcription factor called the aryl hydrocarbon receptor (AHR) that is linked to inflammation suppression and neuroprotection. Untargeted metabolomics of cecal material and plasma revealed that the KD elevated multiple ligands for the AHR, including several indole derivatives of tryptophan catabolism produced exclusively by the gut microbiota. The proposed experiments test the hypothesis that indole derivatives produced by the gut microbiota activate the AHR on optic nerves to promote KD-mediated restoration of vision. Studies include administering the indole derivatives in the drinking water as stand-alone treatments, evaluating KD efficacy in the presence of AHR pharmacological inhibitors and in an AHR ligand-binding mutant mouse strain, and performing longitudinal microbiome analyses to identify the bacterial species enriched by the KD that produce the indole derivatives of interest. Readouts for the above studies include: (a) measuring ocular function by optokinetic tracking, flash visual evoked potentials, and photopic negative response ERGs, (b) measuring indole derivative levels in plasma by GC-MS, (c) quantifying retinal ganglion cell sparing, and (d) quantifying optic nerve (de)myelination, lesion number and size, and AHR target gene expression. Immune cell profiling of optic nerves and spinal cords will reveal the impacts of the KD and the indole derivatives on the balance between pro- and anti-inflammatory immune cell populations. Together, these studies are anticipated to optimize and advance dietary adjuvants that improve visual outcomes for pwMS.


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 = $468,875 )
2026	2026	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Vision Research	000	1	4/17/2026	NEW	$468,875
														Subtotal = $468,875

Grand Total All Awards = $468,875

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanistic investigations of tryptophan catabolites for vision improvement in Multiple Sclerosis

Award Number: R21EY037427

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2026

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