# Nlrp3 inflammasome activation in early diabetic retinopathy

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $484,500

## Abstract

Abstract/Summary
Hallmark pathologic processes of diabetic retinopathy (DR) include neural and glial dysfunction, recruitment of
inflammatory cells, endothelial dysfunction, vascular occlusion, and loss of the blood retinal barrier.
Inflammasomes are innate immune signaling platforms implicated in acute responses to foreign pathogens as
well as numerous chronic neurodegenerative- and inflammatory-related diseases. Inflammasome blockade is
being explored for multiple complex neurovascular conditions including Alzheimer's disease, atherosclerosis,
age-related macular degeneration, and rheumatoid arthritis. Clinical and preclinical evidence suggest that
inflammasome activity may also contribute to pathological hallmarks of DR by promoting production of
inflammatory cytokines, leukostasis, and loss of microvascular integrity. Despite this evidence, major gaps in
knowledge persist with respect to the timing, cellular sources, and pathological implications of inflammasome
activation in the context of diabetic retinopathy. The overall hypothesis of this proposal is that NLRP3
inflammasome activation in circulating immune cells and resident neuroglia drives neuronal and microvascular
dysfunction in diabetic retinopathy. We will test this hypothesis in three specific aims: 1) We seek to identify cell
types that exhibit inflammasome activation and the timing thereof in an animal model of type 1 diabetes; 2) We
seek to determine the contribution of core inflammasome constituents to hallmark pathological phenotypes in
animal models of retinal pathologies due to diabetes. To accomplish this, we will utilize global and cell-specific
genetic knockouts of inflammasome constituents in models of diabetes; 3) We seek to test the efficacy of
pharmacological inflammasome inhibitors in preclinical models of neural, immune, and vascular defects due to
diabetes. Collectively, these thematically related, but independent aims will establish the contribution of
inflammasome in pathological processes of diabetes in the retina. These studies may thereby open new
interventional avenues for this prevalent blinding condition.

## Key facts

- **NIH application ID:** 10051697
- **Project number:** 1R01EY031039-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jayakrishna Ambati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $484,500
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051697

## Citation

> US National Institutes of Health, RePORTER application 10051697, Nlrp3 inflammasome activation in early diabetic retinopathy (1R01EY031039-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051697. Licensed CC0.

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