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Updated: Apr 26, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Hypoxia-hyperoxia paradigms in the development of oxygen-induced retinopathy in a rat pup model
O G Winners-Mendizabal1, F H Orge2, J M Di Fiore3
1All Children's Hospital, St. Petersburg, FL, USA.
Insights
A new intermittent hypoxia/hyperoxia model for retinopathy of prematurity (ROP) in rat pups showed less severe ROP than traditional methods. This model may help study milder ROP in preterm infants.
Area of Science:
- Ophthalmology
- Neonatology
- Animal Models
Background:
- Retinopathy of prematurity (ROP) is a major concern for preterm infants.
- Current animal models for ROP do not fully replicate clinical conditions.
- Understanding hypoxia/hyperoxia roles in ROP pathogenesis is crucial.
Purpose of the Study:
- To develop a clinically relevant animal model for ROP using intermittent hypoxia/hyperoxia (IHH).
- To test if IHH cycles can induce ROP in rat pups, simulating preterm infant environments.
Main Methods:
- Rat pups were exposed to room air (RA), sustained hypoxia/hyperoxia (SHH), or intermittent hypoxia/hyperoxia (IHH) for 14 days.
- Retinae were analyzed at day 18 for avascularization and neovascularization.
- IHH aimed to mimic clinical conditions in preterm infants.
Main Results:
- Sustained hypoxia/hyperoxia (SHH) induced significant retinal avascularity (40.9%).
- Intermittent hypoxia/hyperoxia (IHH) resulted in less avascularity compared to SHH.
- Neovascularization occurred in IHH (5/7 pups) but not in RA, though less severe than in SHH.
Conclusions:
- The IHH protocol, while clinically relevant, produced less severe ROP than the SHH model.
- The IHH model may require refinement but could be valuable for studying milder forms of ROP.
- This study highlights the importance of modeling ROP under conditions closer to clinical settings.
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.
