# Role of Runx1 in Pathologic Ocular Angiogenesis

> **NIH NIH R01** · SCHEPENS EYE RESEARCH INSTITUTE · 2020 · $544,408

## Abstract

PROJECT SUMMARY
Pathologic ocular angiogenesis is the underlying mechanism of a variety of sight threatening diseases of the
eye affecting a wide range of patients including premature infants and the elderly. Retinopathy of prematurity
(ROP), proliferative diabetic retinopathy (PDR), and exudative age-related macular degeneration (wet AMD)
are common causes of blindness in infants, working age, and the elderly respectively. These conditions are
primarily characterized by aberrant neovascularization, or the formation of vascular membranes on top or
below the retina. We performed transcriptome analysis of vascular endothelial cells (ECs) obtained from
fibrovascular membranes (FVMs) from patients with PDR, and identified Runt-related transcription factor 1
(Runx1) as a gene that is upregulated in pathologic ocular angiogenesis. We subsequently showed that Runx1
mediated EC function, and that its inhibition leads to a reduction in aberrant angiogenesis in a mouse model of
oxygen-induced retinopathy (OIR). Based on these data, we hypothesize that Runx1-mediated angiogenesis is
an important mechanism for aberrant angiogenesis within the eye, and that Runx1 inhibition is a potential
therapeutic modality for the treatment of a wide array of pathologic angiogenic diseases. To test this
hypothesis, the following research aims are proposed:
Aim 1. To determine the role of Runx1 in physiological and pathological angiogenesis using genetic
models of Runx1 loss- and gain-of-function: Using inducible models of Runx1 loss- and gain-of-function
(LOF/GOF), we will evaluate the role of Runx1 in both physiological and pathological angiogenesis. We will
look at postnatal development of the retinal vessels, as well as pathologic angiogenesis using laser-induced
choroidal neovascularization (CNV).
Aim 2. To determine the downstream effectors of Runx1 transcriptional activity. Using transcriptome
analysis, we propose to identify genes that are potentially regulated by Runx1 using human retinal
microvascular endothelial cells and Runx1 LOF/GOF models. Using a combination of bioinformatics screening
methodologies (gene ontology analysis, Runx1 regulatory sequence analysis, and comparison to our published
human PDR transcriptomes) and in vitro validation of gene targets, we propose to identify the direct/indirect
downstream mediators that regulate Runx1-mediated angiogenesis.
Aim 3. To compare anti-Runx1 versus anti-VEGF treatment in genetic and inducible models of
pathologic ocular angiogenesis. Anti-Runx1 therapy has potential benefits over anti-VEGF therapy. In this
aim, we propose to compare anti-Runx1 versus anti-VEGF therapy alone or in combination using multiple
models of angiogenesis: OIR, Akimba, and laser-induced CNV. Thus this aim will elucidate the translational
potential of anti-Runx1 therapy for the management of such diseases as ROP, PDR, and wet AMD.

## Key facts

- **NIH application ID:** 9930632
- **Project number:** 5R01EY027739-03
- **Recipient organization:** SCHEPENS EYE RESEARCH INSTITUTE
- **Principal Investigator:** LEO A KIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,408
- **Award type:** 5
- **Project period:** 2018-08-05 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930632

## Citation

> US National Institutes of Health, RePORTER application 9930632, Role of Runx1 in Pathologic Ocular Angiogenesis (5R01EY027739-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9930632. Licensed CC0.

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