Strain-dependent differences in oxygen-induced retinopathy in the inbred rat

Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1445-52. doi: 10.1167/iovs.04-0708.


Purpose: To examine the susceptibilities of different rat strains to oxygen-induced retinopathy, a model of human retinopathy of prematurity.

Methods: Litters of newborn rats of five inbred strains (Fischer 344 [F344], Dark Agouti [DA], Sprague-Dawley [SD], Wistar-Furth [WF], Lewis [LEW]) and one outbred strain (Hooded Wistar [HW]) were maintained in room air or were exposed to alternating 24-hour cycles of hyperoxia (80% oxygen in air) and normoxia (21% oxygen in air) for 14 days and were killed for analysis, either immediately (postnatal day 14, [P14]) or after 4 days in room air (P18). The fluorophore-conjugated isolectin GS-IB4 was used to label the endothelial cells of wholemounted retinas, and digital images were analyzed for avascular area and for morphologic abnormalities.

Results: Exposure to cyclic hyperoxia inhibited retinal vascularization in all strains relative to age-matched room air control animals. Total retinal avascular area at P14 after cyclic hyperoxia varied significantly among strains (P < 0.001). Avascular areas were smallest for the albino F344, WF, and LEW strains; larger for the albino SD strain; and largest for the pigmented DA and HW strains. Susceptibility to hyperoxic vascular attenuation was associated with ocular pigmentation, but neither with body mass nor with natural variation in litter size. Room air exposure for 4 days after cyclic hyperoxia was also associated with strain-related differences in retinal vascularization and with abnormalities in vascular morphology (P < 0.05). For all strains, the size of the avascular retinal area at P14 was predictive of the severity of morphologic abnormality at P18.

Conclusions: Marked and consistent variations in the response of different inbred rat strains to cyclic hyperoxia were observed, suggestive of a genetic component to oxygen-induced retinopathy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Female
  • Fluorescent Dyes / metabolism
  • Humans
  • Hyperoxia / complications*
  • Infant, Newborn
  • Oxygen / toxicity*
  • Plant Lectins / metabolism
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Retinal Neovascularization / etiology*
  • Retinal Neovascularization / genetics
  • Retinal Neovascularization / pathology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / pathology
  • Retinopathy of Prematurity / etiology*
  • Retinopathy of Prematurity / genetics
  • Retinopathy of Prematurity / pathology
  • Species Specificity


  • Fluorescent Dyes
  • Griffonia simplicifolia lectins
  • Plant Lectins
  • Oxygen