# Targeting epithelial membrane protein 2 (EMP2) in retinopathy of prematurity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $405,647

## Abstract

PROJECT SUMMARY
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, affecting approximately 1 in 3-4
extremely low birth weight premature infants. Preterm delivery requires exposing these neonates to relative
hyperoxia because of their lung immaturity. Hyperoxia leads to vessel attenuation in the retina, which results in
local hypoxia, which then fuels abnormal compensatory neovascularization (NV). This process is mediated by
altered expression of growth factors such as vascular endothelial growth factor (VEGF). Though the neuroretina
has been described to play a role in pro-angiogenic signaling in ROP, the mechanisms remain poorly understood.
Current therapies for ROP treat late retinal neovascularization and do not address neuroretinal dysfunction in
ROP. In this grant, we propose to understand the role of an upstream regulator of VEGF, epithelial membrane
protein-2 (EMP2), in an oxygen-induced murine model of retinopathy.
EMP2, a tetraspanin membrane protein important for cell-to-cell signaling, regulates angiogenesis via VEGF and
hypoxia inducible factor (HIF)1α modulation in select cancers and placental diseases. We hypothesize that
EMP2 serves as a regulator of hypoxia-mediated pathological neoangiogenesis in the eye as well. Our
preliminary data from a mouse model of oxygen-induced retinopathy (OIR) demonstrates that genetic knock out
of EMP2 attenuates NV and suppresses HIF1α and VEGFA expression in the neuroretina. Moreover, OIR
induces EMP2 expression in the neuroretina, which in physiologic states, has low expression in the neuroretina
and high expression in the RPE and cornea. However, the role for EMP2 expression and its function in the
developing neuroretina is unknown. The goals of this proposal are to determine the temporal and spatial
expression and function of EMP2 in normal retinal development as well as in pathologic conditions of OIR. Thus,
we seek to understand the mechanisms by which EMP2 regulates neuroretinal angiogenic signaling. We
hypothesize that EMP2 expression, normally isolated to the retinal pigment epithelium (RPE) in the adult mouse
retina, is increased in neuroretinal cells in OIR in the developing eye (Aim 1), where it directly regulates HIF-
mediated VEGF production from these cells (Aim 2). We further hypothesize that antibody-mediated targeting of
EMP2 will safely and effectively attenuate pathologic NV (Aim 3).
Our approach is multidisciplinary, with experts in neonatology/vascular disease in neonates, EMP2 biology,
retinal diseases, genomics, and advanced imaging. We will utilize biochemical, physiological, genomic, and
optical imaging methods in vivo to assess EMP2 expression, function, and the downstream angiogenic effect.
The central innovations of this study are to: (1) further our understanding of the neuroretina’s role in oxygen-
induced retinopathy via EMP2-mediated angiogenic growth factor production, and (2) apply the knowledge of
EMP2’s effects on angiogenesis via VEGF ex...

## Key facts

- **NIH application ID:** 10183025
- **Project number:** 1R01EY032561-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Alison Chu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,647
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183025

## Citation

> US National Institutes of Health, RePORTER application 10183025, Targeting epithelial membrane protein 2 (EMP2) in retinopathy of prematurity (1R01EY032561-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10183025. Licensed CC0.

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