A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat

Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4275-80.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Capillaries / metabolism
  • Capillaries / pathology
  • Disease Models, Animal
  • Endothelial Growth Factors / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Lymphokines / metabolism
  • Oxygen / metabolism*
  • Pregnancy
  • Rats
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*
  • Retinopathy of Prematurity / etiology*
  • Retinopathy of Prematurity / metabolism
  • Retinopathy of Prematurity / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Oxygen