Affiliations: All Children's Hospital, St. Petersburg, FL, USA | Rainbow Babies & Children's Hospital, Cleveland, OH, USA | Case Western Reserve University, Cleveland, OH, USA
Note:  Corresponding author: Dr. Richard J. Martin, Rainbow Babies & Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106-6010, USA. Tel.: +1 216 844 3387; Fax: +1 216 844 3380; E-mail: firstname.lastname@example.org
Abstract: BACKGROUND: Retinopathy of prematurity [ROP] continues to be a significant clinical problem in preterm infants. There is a need for animal models to better understand the roles of hypoxia/hyperoxia in the pathogenesis and management of ROP. OBJECTIVES: To test the hypothesis that multiple daily cycles of intermittent hypoxia, followed by brief hyperoxia, would provide a clinically relevant protocol for generation of ROP in a rat pup. METHODS: Rat pups were exposed for the first 14 days to one of three protocols: room air [RA], sustained cycles of hyperoxia/hypoxia [SHH] as previously employed to produce ROP in rat pups, and intermittent hypoxia/hyperoxia [IHH] in order to more closely simulate clinical conditions in preterm infants. Retinae were obtained at 18 days and imaged for both avascularization and neovascularization. RESULTS: As expected, the SHH group demonstrated significantly increased avascularity [40.9 ± 7.9% of retina] which was minimal in both RA and IHH groups. All SHH exposed pups exhibited neovascularization which occurred in 5/7 IHH exposed retinae versus 0 in the RA group [p = 0.02]. However, mean number of clock hours of neovascularization after IHH was 1.9 ± 2.1 which did not differ from the RA group, and was less than in the SHH group [8.3 ± 1.9, p < 0.001]. CONCLUSION: A more clinically relevant intermittent hypoxia/hyperoxia [IHH] protocol does not produce the same degree of ROP as the traditional sustained hypoxia/hyperoxia [SHH] paradigm. Nonetheless, further refinement of our model may provide a suitable model for understanding the lesser degrees of ROP which predominate in preterm infants.
Keywords: Intermittent hypoxia-hyperoxia, retinopathy of prematurity, rodent model