Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats.

Kay D Beharry,Jacqueline Skelton,Jacob V Aranda,Faisal Siddiqui,Gloria B Valencia,Christina D’Agrosa,Johanna Calo,Charles L Cai

doi:10.3390/ijms19051337

Kay D Beharry, Jacqueline Skelton + Show 6 more

Open Access

https://doi.org/10.3390/ijms19051337

Copy DOI

Abstract

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O2) with brief hypoxia (12% O2); (2) RA with 12% O2; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O2 resolution. Interventions and initiatives to curtail O2 variations should remain a high priority to prevent severe retinopathy.

Highlights

Retinopathy of prematurity (ROP) is a neovascular disease causing childhood blindness worldwide [1]
extremely low gestational age neonates (ELGANs) experiencing the highest incidence of destaturations, bradycardia, and apnea were more vulnerable to malnutrition, extrauterine growth restriction, and nutrient deficits [24], associated with persistent low serum insulin-like growth factor (IGF)-I, which, together with vascular endothelial growth factor (VEGF), plays a crucial role in normal and aberrant retinal angiogenesis and vascular development [25,26,27]
Brain to body weight ratios were lower in all groups at P21, and lung to body weight ratios were lower in all groups except the 50–12% group

Summary

Introduction

Retinopathy of prematurity (ROP) is a neovascular disease causing childhood blindness worldwide [1]. ROP is a developmental vascular disorder caused by abnormal growth of retinal blood vessels in the incompletely vascularized retina of extremely low gestational age neonates (ELGANs) who are

Methods

Results

Conclusion