# Vitreous metabolic perturbations during bacterial and fungal endophthalmitis

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2024 · $487,174

## Abstract

Project Summary
Endophthalmitis is a devastating complication caused by a wide range of microorganisms which can result in
irreversible vision loss if not diagnosed and treated promptly. The current diagnostic approach heavily relies on
microbial culture to determine the etiology of endophthalmitis. However, only ~40% of suspected endophthalmitis
cases are culture-positive, leaving many potentially infectious culture-negative cases. Therefore, the discovery
of potential biomarkers is urgently needed for both the diagnosis of endophthalmitis and in guiding appropriate
antimicrobial therapy. Here, we propose to use metabolomics, an emerging high-throughput technology that can
identify, quantify, and characterize hundreds to thousands of low molecular weight biochemicals (metabolites),
using targeted or untargeted analytical approaches. Since metabolism is directly or indirectly linked to every
aspect of cell function, metabolomics is believed to reflect the phenotype of what is occurring in the body.
Recently, we performed untargeted metabolomics in an experimental model of endophthalmitis and discovered
distinct metabolic profiles of uninfected and bacterial-infected mouse eyes. Moreover, metabolomics analysis
led to discovering a therapeutic target, i.e., itaconate/Irg-1 signaling, to ameliorate experimental bacterial
endophthalmitis. Our pilot vitreous metabolomics analysis showed distinct metabolic profiles in patients with
uveitis, endophthalmitis, and other inflammatory retinal diseases. Based on preliminary data and our prior
publications, we hypothesize that “intraocular infections induce biochemical changes in the vitreous leading to
distinct metabolic signatures with translational potential for therapeutic targeting and/or diagnosis of infectious
endophthalmitis”. This will be tested by performing untargeted metabolomics in vitreous of culture-positive
bacterial and fungal endophthalmitis (Aim-1). We will further devise a metabolic profile to aid in predicting
endophthalmitis in culture-negative chohort. This will be accomplished this by developing an artificial intelligence
(AI) model that can predict endophthalmitis' etiology based on vitreous metabolic profiles (Aim-2). The
experiment will also involve validation using an independent cohort of culture-positive vitreous. The proposed
study will be the first to utilize metabolomics profiling to identify the metabolic sigantures in the vitreous of
endophthalmitis patients. The resulting profiles and/or biomarkers will be readily translatable for future clinical
studies, ultimately guiding precision medicine for diagnosing and treating ocular infections.

## Key facts

- **NIH application ID:** 10990855
- **Project number:** 1R01EY035499-01A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Ashok Kumar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $487,174
- **Award type:** 1
- **Project period:** 2024-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990855

## Citation

> US National Institutes of Health, RePORTER application 10990855, Vitreous metabolic perturbations during bacterial and fungal endophthalmitis (1R01EY035499-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10990855. Licensed CC0.

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