Hyperoxia-induced endothelial cell dysfunction: investigating the role of FBXW7

Abstract

Retinopathy of prematurity (ROP) is a sight-threatening disease affecting premature infants and is driven by abnormal retinal vascular development in response to fluctuating oxygen exposure. The early hyperoxic phase disrupts normal vascular growth, leading to later hypoxia-driven pathological neovascularisation. Despite its clinical importance, molecular regulators of endothelial responses to hyperoxia remain incompletely understood.

Transcriptomic screening identified FBXW7, a component of the SCF E3 ubiquitin ligase complex, as a candidate regulator of oxidative stress responses in retinal endothelial cells (EC). This study investigated the regulation of FBXW7 and its potential role in retinal vascular dysfunction using EC models and the oxygen-induced retinopathy (OIR) mouse model.

The findings demonstrate that FBXW7 is dynamically regulated in EC and during retinal vascular development under oxygen stress conditions. These results implicate FBXW7-associated pathways in endothelial responses relevant to ROP and highlight them as potential targets for future therapeutic investigation.

Thesis is embargoed until 31 July 2031.

Date of Award	Jul 2026
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Fight for Sight (Inc British Eye Research Foundation)
Supervisor	Denise McDonald (Supervisor) & Paul Moynagh (Supervisor)