A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat.
OBJECTIVE
To examine changes in the retinal vasculature of rat pups after 14 days of minute-by-minute small variations in oxygen.


METHODS
Arterial oxygen data from a preterm infant who developed severe retinopathy of prematurity (ROP) was translated to equivalent values for the rat. Newborn rat pups were raised for 14 days in a cage in which a computer controlled the atmosphere to mimic the fluctuating oxygen profile (group V). Positive controls (P) of 12-hour cycles of 80% and 21% were run concurrently, as were room air controls (C). All were killed at day 14.


RESULTS
Groups V and P had significantly larger avascular retinal areas than C [median, interquartile range (IQR) 1.7%, 0-7.9%; 10%, 8.1-13%; 0%, 0-0%, respectively; each group n = 30]. Group P had a higher capillary branch count than C (median, IQR: 310/mm(2); 253-311 mm(2); versus 277/mm(2), 272-364/mm(2), respectively), but this was not significant using a multilevel analysis. Group V had significantly reduced capillary counts compared with C (median, 261/mm(2); IQR, 215-290/mm(2); P < 0.05 multilevel analysis). No neovascularization was seen in any group, though abnormal terminal vessels were seen at the avascular/vascular retina interface in 73% of rats in group P and 21% of rats in group V. In situ hybridization on serial sections demonstrated VEGF in the inner nuclear layer of the retina in P and V, whereas C showed trace levels only.


CONCLUSIONS
The vaso-obliterative stage of ROP can be induced in rats using clinically relevant oxygen levels.
Cunningham
S
S
Child Life and Health, Reproductive and Developmental Sciences, University of Edinburgh. Princess Alexandra Eye Pavilion, Edinburgh, Scotland, United Kingdom.
McColm
J R
JR
Wade
J
J
Sedowofia
K
K
McIntosh
N
N
Fleck
B
B
D000818:Animals; D000831:Animals, Newborn; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010100:Oxygen