# Mechanisms of Retinal Vascular Permeability in Diabetes

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $411,799

## Abstract

ABSTRACT
Diabetes mellitus remains a leading cause of blindness world-wide and epidemiological data
from the World Health Organization reveal over 422 million adults live with diabetes and the rate
of disease onset continues to rise. According to the National Eye Institute 10.2 million US adults
40 years and older have diabetes mellitus, and 8.2% with vision threatening retinopathy.
Macular edema remains closely linked to loss of vision and current therapies focus on
mechanisms to prevent cytokine driven changes in vascular permeability that promote edema.
Our previous research has fundamentally contributed to understanding the molecular
mechanisms that lead to vascular endothelial growth factor (VEGF) induced retinal vessel
permeability. The development of effective anti-VEGF therapies has been a welcome addition
for the treatment of diabetic retinopathy, but this approach remains insufficient and new
therapies are needed. In the current application we now focus on understanding the process of
blood-retinal barrier regeneration. Research has identified a required role for norrin in formation
of the blood-retinal barrier. Here, we explore the exciting potential for norrin to restore vascular
barrier properties after VEGF-induced injury. The studies promise to shed new light on how
these two critical cytokines interact to control retinal vessel barrier properties. Further,
preliminary data reveal completely novel interactions of the norrin signaling molecule,
disheveled (DVL), binding directly to tight junction proteins. The role of these protein interactions
on norrin signaling and tight junction biology will be elucidated at a molecular level in order to
understand the mechanisms of norrin action on barrier restoration. We expect this proposal will
provide novel information on regulation of the blood-retinal barrier in health and in diabetes and
will provide a framework from which to develop potential new therapeutic options to treat
macular edema.

## Key facts

- **NIH application ID:** 10463572
- **Project number:** 5R01EY012021-24
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** David Antonetti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $411,799
- **Award type:** 5
- **Project period:** 1998-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463572

## Citation

> US National Institutes of Health, RePORTER application 10463572, Mechanisms of Retinal Vascular Permeability in Diabetes (5R01EY012021-24). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10463572. Licensed CC0.

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