# A Diabetic Retinopathy-Associated Vascular Permeability Factor

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $388,002

## Abstract

Project Summary
Diabetic retinopathy (DR) is a leading cause of vision loss, affecting nearly 100 million people worldwide.
Vascular leakage factors and angiogenic factors play an important role in the pathogenesis of vision-threatening
diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR), respectively. Vascular endothelial
growth factor (VEGF) inhibitors have been approved for DME but not PDR with limited therapeutic efficacy.
Identification of additional pathological ligands may lead to development of novel therapies for DME and PDR.
We recently discovered secretogranin III (Scg3) as a highly disease-associated pro-angiogenic factor that
preferentially binds to and stimulates angiogenesis of diabetic but not normal vessels. In contrast, VEGF binds
to and induces angiogenesis of both diabetic and normal vessels. Among thousands of quantified endothelial
ligands, Scg3 has the highest binding activity ratio to diabetic vs. control retinal vessels but the lowest binding to
normal vasculature. Unlike VEGF upregulation in PDR, however, Scg3 expression minimally increases in
diabetic retina. This project is to investigate a new pathogenic mechanism by which the upregulation of Scg3
selective binding to diseased vessels, but not ligand expression itself, exacerbates DR pathogenesis. In Aim 1,
we will quantify and correlate Scg3 disease-related endothelial binding activity to the severity of DR leakage. In
Aim 2, we will establish a correlation between Scg3 endothelial binding activity and the severity of pathological
retinal neovascularization in mice. In Aim 3, a well-characterized Scg3-neutralizing monoclonal antibody with
high therapeutic efficacy and safety will be humanized and analyzed for its activity to alleviate DR leakage and
pathological retinal neovascularization. To our knowledge, Scg3 is the first highly selective angiogenic factor.
Investigation of Scg3 and its pathogenic mechanism will facilitate the discovery and characterization of other
ligands with similar disease selectivity. Humanization of anti-Scg3 antibody may lead to the development of a
new class of “selective angiogenesis blockers” for the therapy of DR and other retinal vascular diseases.

## Key facts

- **NIH application ID:** 10210399
- **Project number:** 5R01EY027749-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Wei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,002
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210399

## Citation

> US National Institutes of Health, RePORTER application 10210399, A Diabetic Retinopathy-Associated Vascular Permeability Factor (5R01EY027749-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10210399. Licensed CC0.

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