# Redox-dependent signaling in hyperoxia-induced retinal vascular arrest

> **NIH NIH R21** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 · $210,975

## Abstract

PROJECT SUMMARY
Retinopathy of prematurity (ROP) is caused by retinal vascular growth arrest followed by compensatory
dependent aberrant neovascularization during exposure to supplemental oxygen given to treat respiratory
distress in preterm infants. Since oxygen tension is critical for both vascular arrest and neovascularization
phases of ROP, defining oxygen-dependent signaling pathways in retinal endothelial cells is a critical barrier
for understanding ROP pathogenesis, identification of novel therapeutic targets, and optimization of the
postnatal care environment. Reversible oxidation of protein thiols facilitates signaling during redox
perturbations including changes in oxygen tension (e.g. hyperoxia, hypoxia). Protein thiol oxidation is
regulated, in part, through the thiol oxidoreductase activities of dedicated redox enzymes such as thioredoxin 1
(Trx1) and an endogenous inhibitor of Trx1, thioredoxin interacting protein (Txnip). Suggestive that the thiol
proteome is altered during hyperoxic-dependent vascular growth arrest, retinal expression of Trx1 and Txnip
increases in an experimental model of ROP and Txnip-deficient mice have increased vaso-obliteration and
expression of apoptotic markers. Therefore, this project tests the hypothesis that the Trx1:Txnip axis serves as
a molecular sensor of redox perturbations to influence hyperoxia-induced retinal vascular arrest during ROP.
The following specific aims utilize genetic and molecular approaches in an experimental mouse model of ROP
to investigate roles of Trx1 and Txnip in hyperoxic-dependent vascular growth arrest associated with ROP and
identify oxygen-dependent signaling pathways in retinal endothelium: (Aim 1) Determine if Trx1 & Txnip
expression influences ROP-induced vascular arrest, and (Aim 2) Define oxygen-sensitive, Trx1-dependent
signaling pathways in retinal endothelial cells. Successful completion of this project will accelerate the
discovery of oxygen-dependent signaling pathways in retinal endothelial cells, harness information for
understanding ROP pathogenesis, and improve development of new therapeutic and clinical care approaches
to ameliorate ROP outcomes.

## Key facts

- **NIH application ID:** 10486128
- **Project number:** 5R21EY033075-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Faizah Naheed Bhatti
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $210,975
- **Award type:** 5
- **Project period:** 2021-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10486128

## Citation

> US National Institutes of Health, RePORTER application 10486128, Redox-dependent signaling in hyperoxia-induced retinal vascular arrest (5R21EY033075-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10486128. Licensed CC0.

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