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Updated: May 30, 2026
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Early retinal blood vessel growth in normal and growth restricted rat pups raised in oxygen and room air
C A Dhaliwal1, J Wade, T Gillespie
1Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
Insights
Growth restriction and fluctuating oxygen worsen retinal avascularity in premature infants, increasing retinopathy of prematurity risk. This study developed a rat model to investigate these factors in retinal vascular development.
Area of Science:
- Ophthalmology
- Developmental Biology
- Neonatology
Background:
- Premature infants face retinopathy of prematurity (ROP) risk due to underdeveloped retinal vasculature.
- Prenatal and postnatal growth rates significantly influence ROP development.
- Current models lack the complexity to fully replicate ROP pathogenesis.
Purpose of the Study:
- To establish a physiology-based rat model for studying ROP.
- To investigate the combined impact of growth restriction and fluctuating oxygen on retinal vascular development.
- To provide a tool for understanding ROP's early pathogenesis.
Main Methods:
- Rat mothers received diets inducing intrauterine growth restriction (9% casein).
- Pups were exposed to fluctuating hyperoxic oxygen profiles postnatally.
- Retinal avascular areas were quantified using microscopy on postnatal day 14.
Main Results:
- Growth-restricted pups exhibited significantly larger avascular retinal areas compared to controls.
- Fluctuating oxygen exposure exacerbated avascularity in growth-restricted pups.
- The model demonstrated a clear link between growth, oxygen, and retinal vascular development.
Conclusions:
- A novel rat model successfully replicates key ROP risk factors: growth restriction and fluctuating oxygen.
- This model allows for detailed study of how growth, nutrition, and oxygen affect early retinal vascularization.
- The findings underscore the importance of addressing growth and oxygen environments in ROP prevention.
Background/Aims:
Premature infants are born with incompletely vascularised retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of prenatal and postnatal body growth is important in the pathogenesis of ROP. The aim of this study was to develop a physiology-based rat model in order to study the effect of growth restriction and oxygen on early retinal vascular development.
Methods:
Rat mothers were fed either a normal (18% casein) or low (9% casein) protein diet (to cause pup growth restriction) from the last week of gestation. After birth, mother and pups were placed in either room air or a specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen profile. The oxygen profile was based on that from a premature infant who developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained using biotinylated lectin. Images were captured by confocal microscopy. The avascular areas of the retinas were measured and compared.
Results:
Growth restricted rat pups had significantly larger retinal avascular areas than 'normally grown' rat pups (Mann-Whitney U test, p<0.001). Growth restricted rat pups raised in fluctuating oxygen had significantly larger retinal avascular areas than growth restricted rat pups raised in room air (Mann-Whitney U test, p=0.001).
Conclusions:
The authors have developed a novel model for ROP that involves inducing both intrauterine and postnatal growth restriction and also exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can be used to study the effects of growth, nutrition and oxygen on early retinal vascular development.
