Early retinal blood vessel growth in normal and growth restricted rat pups raised in oxygen and room air.

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.