Modification and evaluation of ameliorative oxygen-induced retinopathy mouse model

Authors: Liu Aihua,  Sun Jing,  Zhang Hong
DOI: 10.3760/cma.j.issn.2095-0160.2015.12.012
Published 2015-12-10
Cite as Chin J Exp Ophthalmol, 2015,33(12): 1108-1112.

Abstract                            [Download PDF] [Read Full Text]


Retinal neovascularization is associated with various disorders.Studying the pathogenesis of retinal neovascularization is of important significance.Oxygen-induced retinopathy(OIR) mouse model is a common animal model for the study of retinal neovascular diseases.However, conventional modeling methods usually cause high animal mortality and low rate of success.


This study aimed to establish a modified method of mouse OIR model.


Eighty 1-week-old SPF C57BL/6J mice were randomly divided into normal control group and OIR group with 40 mice for each.The newborn mice of the normal control group were kept in a normal air environment with their breast-feeding mothers, but the mice of postnatal 2 days (P2) in the OIR group were raised with two litters per cage until P7.The P7 mice exposed to oxygen tank containing 80% oxygen together with one or another mother mouse alternately daily for 5 days and then returned to the normal air environment.The success rate of modeling, mortality rate of maternal mice and survival rate of immature mice were evaluated.The mixed solution of fluorescein isothiocyanate (FITC) and PBS with 4% paraformaldehyde was infused into the hearts of P12, P14, P17 and P21 mice and the eyeballs were obtained after the mice were sacrificed for histopathological examination of retinas and preparation of retinal flatmounts.The number of vascular endothelial cells extending inner limiting membrane was counted and the distribution of retinal vessels was evaluated.The use and care of the animals complied with the Statement of ARVO.


The survival rate of the neonatal mice was 100% both in the normal control group and the OIR group, and the survival rate of maternal mice was 85.7% in the OIR group.Retinal new vessels were found in the mice of the OIR group, with the success rate of modeling 100%.The retinal vessels distributed from optical disc toward periphery in P14 mice in the normal group.However, in the OIR group, non-perfusion area at the posterior pole was seen in P12 mice, new blood vessels at the periphery were found in P14 mice, neovascularization at the junction area between vascular area and non-perfusion area as well as leakages were exhibited in P17 mice, and less non-perfusion area and new vessels were seen in P21 mice.Retinal inner limiting membrane was smooth in the mice of the normal group, and the vascular endothelial cell nucleus extending inner limiting membrane were seen in P12 mice and peaked in P17 mice.The vascular endothelial cell nucleus were (11.44±2.01), (31.24±1.50) and (9.23±1.12)/slide in P14, P17 and P21 mice in the OIR group, which were significantly more than (0.27±0.14), (0.30±0.11) and (0.32±0.16)/slide in P14, P17 and P21 mice in the normal group (t=47.90, 61.30, 40.70, all at P<0.05).


The method of OIR modeling is modified by alternating maternal mice, exposing to 80% oxygen-nitrogen mixture gas and cohabitating immature mice.Modified modeling method is simple with the low death rate of maternal mice and stable OIR phenotype.

Key words:

Retinal neovascularization/pathology; Retinal diseases/oxygen induced; Oxygen/toxicity; Disease models, animal; Angiogenesis; Mice, inbred C57BL/6J

Contributor Information

Liu Aihua
Tianjin Medical University Eye Hospital, School of Optometry and Ophthalmology, Tianjin Medical University, Tianjin Medical University Eye Institute, Tianjin 300384, China
Sun Jing
Zhang Hong
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Updated: February 27, 2023 — 7:21 am