# Ocular Inflammatory Mediators in the Pathophysiology of Diabetic Retinopathy

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $419,525

## Abstract

Project Summary
Diabetic retinopathy (DR) is a major cause of blindness worldwide. DR progresses in many patients despite
preventable measures such as blood sugar and blood pressure control. Other available treatments require
invasive eye injections and are often ineffective—DR remains the leading cause of legal blindness among
working-age adults. Current diagnostic tests fail to identify early disease stages or predict disease progression.
Consequently, new biomarkers and therapeutic strategies are needed.
DR is an established inflammatory disease with leukocyte involvement. Many inflammatory cytokines (products
of leukocytes) are consistently elevated in the aqueous and vitreous of patients with advanced DR and diabetic
macular edema (DME). Inflammatory mediators are candidates for direct biomarkers that may predict DR
progression as well as treatment response. To date the only validated prognostic DR biomarker is the
circulating glycemia marker glycated hemoglobin (HbA1C). HbA1C screening, however, reflects glucose
control, which indicates disease risk as opposed to DR pathology.
Our central hypothesis is that intraocular inflammatory mediators such as PGE2, IL-6, and IL-8 are markers of
DR severity and therefore predict risk of disease progression. Equally important, they represent potential novel
targets for inhibition. We have recently demonstrated that topically applied ketorolac, a nonsteroidal anti-
inflammatory drug, achieves therapeutic vitreous levels and significantly reduces several elevated
inflammatory mediators in eyes with DR. These observations and its commercial availability provide rationale to
investigate the relationship of inflammatory mediators with DR severity and the long-term effects of chronic
topical administration of ketorolac in diabetic patients.
Our current goals include confirming inflammation mediators are biomarkers of both systemic diabetes and DR
progression in the aqueous. Like the vitreous humor, the aqueous reflects localized ocular inflammation,
however, is technically easier to collect with less risk. We will also determine the long-term effects of sustained
ketorolac application on intraocular cytokine levels, DR progression, and DME incidence. Our proposal is the
first to use a cornea-permeable NSAID for the treatment of DR.
We believe local inflammation control in the eye will transform future treatment options for diabetic patients
facing blindness. Tracking and inhibiting local inflammatory mediators through all DR stages has the capacity
to reduce or prevent disability in millions of patients per year.

## Key facts

- **NIH application ID:** 10480946
- **Project number:** 5R01EY031315-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Stephen Jae Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $419,525
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480946

## Citation

> US National Institutes of Health, RePORTER application 10480946, Ocular Inflammatory Mediators in the Pathophysiology of Diabetic Retinopathy (5R01EY031315-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10480946. Licensed CC0.

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