Retinopathy of Prematurity Protection Conferred by Uteroplacental Insufficiency Through Erythropoietin Signaling in an Experimental Murine Model

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2023 Apr 4

PMID 37016003

Authors

Camille Fung

Thaonhi Cung

Caroline Nelson

Haibo Wang

Colin Bretz

Aniket Ramshekar

Ashley Brown

Gregory J Stoddard

M Elizabeth Hartnett

Affiliations

Soon will be listed here.

Abstract

Background: Recent clinical studies suggest that preeclampsia, characterized by uteroplacental insufficiency (UPI) and infant intrauterine growth restriction (IUGR), may be protective against retinopathy of prematurity (ROP) in preterm infants. Experimental models of UPI/IUGR have found an association of erythropoietin (EPO) with less severe oxygen-induced retinopathy (OIR); however, it is unclear if EPO/EPO receptor (EPOR) signaling was involved. We hypothesized that maternal UPI and resultant infant IUGR would protect against features of ROP through EPO/EPOR signaling.

Methods: We compared transgenic mice with hypoactive EPOR signaling (hWtEPOR) to littermate wild-type mice (mWtEpoR) in a novel combined model of IUGR and ROP. Thromboxane A (TXA) was infused into pregnant C57Bl/6J dams to produce UPI/IUGR; postnatal pups and their foster dams were subjected to a murine OIR model.

Results: Following hyperoxia, hematocrits were similar between littermate wild-type (mWtEpoR) TXA2/OIR and vehicle/OIR pups. mWtEpoR TXA/OIR had increased serum EPO, retinal EPO and VEGF, and decreased avascular retinal area (AVA) compared to vehicle/OIR pups. In comparison to the mWtEpoR TXA/OIR pups, AVA was not reduced in hWtEPOR TXA/OIR pups.

Conclusion: Our findings provide biologic evidence that UPI/OIR-induced endogenous EPOR signaling confers protection against hyperoxia-induced vascular damage that may be related to pathophysiology in ROP.

Impact: Maternal preeclampsia and infant growth restriction confer retinovascular protection against high oxygen-induced damage through endogenous erythropoietin signaling.

Citing Articles

Association between hematocrit in the first two hours of life and retinopathy during prematurity: a retrospective study from DRYAD.

Kong X, Wang H, Yang R, Zhang M, Li C, Zhang R BMC Pediatr. 2025; 25(1):176.

PMID: 40057690 PMC: 11889788. DOI: 10.1186/s12887-025-05533-8.

Enhancing the Retinopathy Of Prematurity Risk Profile Through Placental Evaluation of Maternal and Fetal Vascular Malperfusion.

El Emrani S, Jansen E, Goeman J, Termote J, Lopriore E, Schalij-Delfos N Invest Ophthalmol Vis Sci. 2024; 65(11):9.

PMID: 39230991 PMC: 11379085. DOI: 10.1167/iovs.65.11.9.

Editorial: Identification of novel biomarkers for retinopathy of prematurity in preterm infants by use of innovative technologies and artificial intelligence.

Slidsborg C, Fielder A, Hartnett M Front Pediatr. 2024; 12:1382858.

PMID: 38510080 PMC: 10951073. DOI: 10.3389/fped.2024.1382858.

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