Endothelial Cell Specific Thioredoxin 1-Dependent Signaling in Oxygen-1 Induced Retinopathy
- 1University of Oklahoma Harold Hamm Health Campus
Abstract
Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, characterized byoxidative stress and dysregulated angiogenesis in preterm infants with immature antioxidant systems.This study aimed to investigate the specific role of endothelial cell-specific thioredoxin 1 (TXN1), a crucial oxidoreductase, in oxygen-induced retinopathy, hypothesizing that the absence of endothelial TXN1 directly impairs angiogenesis and exacerbates hyperoxia-induced injury. Methods: We generated tamoxifen-inducible, endothelial cell-specific Txn1 knockout mice (Txn1-iECKO) and utilized the oxygen-induced retinopathy (OIR) model, exposing litters to 85% oxygen from postnatal day 7 (P7) to P12. Retinal vascular morphology during vaso-obliteration and neovascularization phases, endothelial cell proliferation, and apoptotic cell death were assessed. Furthermore, human retinal microvascular endothelial cells (HRMECs) with TXN1 knockdown were subjected to hyperoxic conditions, followed by comprehensive gene expression profiling using RT2 Profiler PCR arrays and Ingenuity Pathway Analysis. Results: Deletion of endothelial Txn1 significantly enhanced vascular regression during the hyperoxic vaso-obliteration phase at P12 and markedly exacerbated pathological neovascularization at P17. Txn1-deficient retinas exhibited significantly impaired endothelial cell proliferation during the vaso-obliteration phase, while apoptotic cell death remained unchanged. Transcriptomic analysis of TXN1-deficient HRMECs under hyperoxia revealed an enhanced activation of NRF2-mediated oxidative stress response pathways. Conclusions: These findings identify endothelial TXN1 as an essential and oxygen-dependent regulator of vascular development in ischemic retinopathy, primarily influencing endothelial proliferation and redox signaling. This suggests TXN1's crucial protective role and highlights its therapeutic potential to mitigate ROP progression by modulating endothelial cell responses to oxidative stress.
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BibTeX
@misc{song2026endothelial,
title = {{Endothelial Cell Specific Thioredoxin 1-Dependent Signaling in Oxygen-1 Induced Retinopathy}},
author = {H. Song and W. Wu and D. Khan and H. Zhong and M. Meaders and P. T. Pierce and P. F. Vitiello and L. Rogers and T. E. Tipple and F. N. Bhatti},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.763768},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.763768v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Endothelial Cell Specific Thioredoxin 1-Dependent Signaling in Oxygen-1 Induced Retinopathy
AU - H. Song
AU - W. Wu
AU - D. Khan
AU - H. Zhong
AU - M. Meaders
AU - P. T. Pierce
AU - P. F. Vitiello
AU - L. Rogers
AU - T. E. Tipple
AU - F. N. Bhatti
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.763768
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.763768v1
AB - Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, characterized byoxidative stress and dysregulated angiogenesis in preterm infants with immature antioxidant systems.This study aimed to investigate the specific role of endothelial cell-specific thioredoxin 1 (TXN1), a crucial oxidoreductase, in oxygen-induced retinopathy, hypothesizing that the absence of endothelial TXN1 directly impairs angiogenesis and exacerbates hyperoxia-induced injury. Methods: We generated tamoxifen-inducible, endothelial cell-specific Txn1 knockout mice (Txn1-iECKO) and utilized the oxygen-induced retinopathy (OIR) model, exposing litters to 85% oxygen from postnatal day 7 (P7) to P12. Retinal vascular morphology during vaso-obliteration and neovascularization phases, endothelial cell proliferation, and apoptotic cell death were assessed. Furthermore, human retinal microvascular endothelial cells (HRMECs) with TXN1 knockdown were subjected to hyperoxic conditions, followed by comprehensive gene expression profiling using RT2 Profiler PCR arrays and Ingenuity Pathway Analysis. Results: Deletion of endothelial Txn1 significantly enhanced vascular regression during the hyperoxic vaso-obliteration phase at P12 and markedly exacerbated pathological neovascularization at P17. Txn1-deficient retinas exhibited significantly impaired endothelial cell proliferation during the vaso-obliteration phase, while apoptotic cell death remained unchanged. Transcriptomic analysis of TXN1-deficient HRMECs under hyperoxia revealed an enhanced activation of NRF2-mediated oxidative stress response pathways. Conclusions: These findings identify endothelial TXN1 as an essential and oxygen-dependent regulator of vascular development in ischemic retinopathy, primarily influencing endothelial proliferation and redox signaling. This suggests TXN1's crucial protective role and highlights its therapeutic potential to mitigate ROP progression by modulating endothelial cell responses to oxidative stress.
ER -