451. A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat.
- Author
-
Cunningham S, McColm JR, Wade J, Sedowofia K, McIntosh N, and Fleck B
- Subjects
- Animals, Animals, Newborn, Capillaries metabolism, Capillaries pathology, Disease Models, Animal, Endothelial Growth Factors metabolism, Female, Humans, Immunoenzyme Techniques, In Situ Hybridization, Infant, Newborn, Lymphokines metabolism, Pregnancy, Rats, Retinal Vessels metabolism, Retinopathy of Prematurity metabolism, Retinopathy of Prematurity pathology, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Infant, Premature metabolism, Oxygen metabolism, Retinal Vessels pathology, Retinopathy of Prematurity etiology
- Abstract
Purpose: 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.
- Published
- 2000