# Cell-Meditated Inflammatory Pathway and Diabetic Retinopathy

> **NIH NIH R15** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2022 · $355,110

## Abstract

Retinal pericytes are contractile cells adjacent to and provide support for endothelial cells of
capillaries, which are essential in the regulation of retinal vasculature in the eye. Early stages of
diabetic retinopathy are characterized by the loss of retinal pericytes, which lead to the
development of advanced-stage pathology including angiogenesis. Although much is known
about the etiology of diabetic retinopathy, the apoptotic pathway that incites retinal pericyte loss
remains unclear. Our preliminary studies reveal that monocyte-derived macrophages secrete
TGFβ1, which induces the expression and secretion of a TGFβ1-Induced, pro-apoptotic BIGH3
protein (TGFβ –Induced Gene Human Clone 3) leading to apoptosis of endothelial cells and
retinal pericytes. This cascade of events has been attributed to the primary cause of retinal
pericyte apoptosis and diabetic retinopathy. Macrophage TGF-β1 and BIGH3 are prediabetic
biomarkers, and potential therapeutic targets for intervention of diabetic retinopathy for diabetic
individuals. In the present study, we hypothesize that a similar macrophage-TGFβ–BIGH3
pathway may induce apoptosis in retinal pericytes. We will investigate the interaction between
endothelial cells and retinal pericytes, as well as macrophages’ role on retinal pericyte expression
of BIGH3 in response to TGFβ, and retinal pericyte apoptosis. Furthermore, we will also study
the association of BIGH3 with integrin, a trans-membrane signaling protein receptor and its role
to mediate retinal pericyte apoptosis. This novel study focuses on macrophage-mediated
molecular pathway to impact diabetic retinopathy and it will provide opportunities of therapeutic
intervention of this ocular eye disorder. Student trainees will be involved in these research
projects, providing valuable experience on biomedical research.

## Key facts

- **NIH application ID:** 10368669
- **Project number:** 1R15EY033551-01
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** ANDREW T C TSIN
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,110
- **Award type:** 1
- **Project period:** 2022-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368669

## Citation

> US National Institutes of Health, RePORTER application 10368669, Cell-Meditated Inflammatory Pathway and Diabetic Retinopathy (1R15EY033551-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10368669. Licensed CC0.

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