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Updated: May 9, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
A murine model for retinopathy of prematurity identifies endothelial cell proliferation as a potential mechanism for
Victor H Guaiquil1, Nina J Hewing, Michael F Chiang
1Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021, USA.
Insights
This study characterizes plus disease in a mouse model of retinopathy of prematurity. Increased vascular cell proliferation drives plus disease, and ADAMs 8, 9, and 10 may be therapeutic targets.
Area of Science:
- Ophthalmology
- Vascular Biology
- Developmental Biology
Background:
- Retinopathy of prematurity (ROP) is a leading cause of childhood blindness.
- Plus disease, characterized by retinal vascular abnormalities, is a key indicator of ROP severity.
- Understanding the mechanisms of plus disease is crucial for developing effective treatments.
Purpose of the Study:
- To characterize the features and underlying mechanisms of plus disease in a mouse oxygen-induced retinopathy (OIR) model.
- To investigate the role of A Disintegrin And Metalloproteinases (ADAMs) in the development of plus disease.
Main Methods:
- Mice were exposed to hyperoxia followed by relative hypoxia to induce OIR.
- Live fundus imaging, fluorescein angiography, and immunofluorescence were used to analyze retinal vascular changes.
- Arterial tortuosity, venous dilation, and endothelial cell proliferation (using BrdU labeling) were quantified.
Main Results:
- The OIR model successfully replicated key features of plus disease, including arterial tortuosity and venous dilation.
- These vascular abnormalities and endothelial cell proliferation increased over time post-OIR.
- Mice lacking ADAM8, ADAM9, or endothelial ADAM10 showed partial protection against plus disease.
Conclusions:
- The mouse OIR model is suitable for studying plus disease pathogenesis and identifying therapeutic targets.
- Increased endothelial cell proliferation is a likely mechanism driving plus disease development.
- ADAMs 8, 9, and 10 represent potential therapeutic targets for treating plus disease in ROP.
Purpose:
To characterize the features and possible mechanism of plus disease in the mouse oxygen-induced retinopathy (OIR) model for retinopathy of prematurity.
Methods:
Wild-type and Adam (A Disintegrin And Metalloproteinase) knockout mice were exposed to 75% oxygen from postnatal day 7 to 12 (P7 to P12) (hyperoxia), then returned to normal air (relative hypoxia). Live fundus imaging and fluorescein angiography at P17 were compared to immunofluorescence analysis of flat-mounted retinas. Two hallmarks of plus disease, arterial tortuosity and venous dilation, were analyzed on fixed retinas (P12-P17). The length of tortuous vessels was compared to a straight line between two points; the diameter of retinal vessels was determined using ImageJ software, and bromo-deoxyuridine (BrdU) labeling was used to visualize proliferation of retinal vascular cells.
Results:
Mice developed retinal arterial tortuosity and venous dilation after exposure to OIR, which was visible in live fundus images and fixed whole-mounted retinas. Vein dilation, arterial tortuosity, and BrdU incorporation gradually increased over time. Moreover, Adam8(-/-) and Adam9(-/-) mice and mice lacking Adam10 in endothelial cells were partially protected from plus disease compared to controls.
Conclusions:
The mouse OIR model can be used to study the pathogenesis of plus disease and identify potential therapeutic targets. The severity of plus disease increases over time following OIR and correlates with increased proliferation of endothelial cells, suggesting that proliferation of vascular cells may be a mechanism underlying the development of plus disease. Moreover, our findings suggest that ADAMs 8, 9, and 10 could be targets for treatment of plus disease.
