# The role of Tbx3 in retinal angiogenesis and eye disease

> **NIH EY R01** · UPSTATE MEDICAL UNIVERSITY · 2026 · $417,745

## Abstract

Patients with neovascular disease, including Retinopathy of Prematurity and Familial Exudative
Vitreoretinopathy (FEVR), develop insufficiently vascularized, or hypovascular, retinas. We have observed a
similar hypovascular phenotype in the Tbx3 conditional knockout retina. Our long-term goal is to understand
how retinal neurons and vascular cells form the neurovascular unit. The objective of this proposal is to
determine the role Tbx3 plays in retinal angiogenesis as a way to uncover new molecular mechanisms driving
retinal vascular disease. In our model, TBX3 is required during three events that are essential for retinal
angiogenesis, when 1) retinal ganglion cells become metabolically active, causing retinal astrocytes to
proliferate; 2) the embryonic hyaloid vasculature regresses in response to increases in dopamine levels; and 3)
astrocytes migrate into the retina to form the astrocytic lattice. Our central hypothesis is that TBX3 regulates
signals that affect retinal angiogenesis via its regulation in three separate cell types: first, in dorsal retinal
ganglion cells, next, in dopaminergic amacrine cells, and finally, in astrocytes. The rationale underpinning this
hypothesis is that key genetic networks controlling neurogenesis and angiogenesis are shared and thereby
coordinate neurovascular coupling. We will test the central hypothesis by determining the TBX3-regulated
molecular mechanisms that affect angiogenesis in 1) dorsal retinal ganglion cells via Sonic Hedgehog
signaling, 2) dopaminergic amacrine cells via regulation of tyrosine hydroxylase, and 3) retinal astrocytes via
control of migration. Each of these aims will be pursued using a combination of large-scale transcriptomic
studies coupled with genetic manipulation and molecular analysis, which are standard technologies in our lab.
Our studies are significant because they will fill a major gap in knowledge about vascular formation and identify
new molecular pathways activated during angiogenesis. The

## Key facts

- **NIH application ID:** 11345644
- **Project number:** 5R01EY033910-03
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** ANDREA S VICZIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** EY
- **Fiscal year:** 2026
- **Award amount:** $417,745
- **Award type:** 5
- **Project period:** 2024-05-01T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11345644

## Citation

> US National Institutes of Health, RePORTER application 11345644, The role of Tbx3 in retinal angiogenesis and eye disease (5R01EY033910-03). Retrieved via AI Analytics 2026-06-30 from https://api.ai-analytics.org/grant/nih/11345644. Licensed CC0.

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