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Updated: Jul 11, 2026

Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Interaction between iNOS and COX-2 in hypoxia-induced retinal neovascularization in mice
Tao He1, Yi-Qiao Xing, Xiao-Hui Zhao
1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.
Background:
Upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) has been reported in hypoxia-induced retinal angiogenesis. The aim of our study was to evaluate the possible interaction between the COX and NOS pathways and the effect of this interaction on matrix metalloproteinases 2 (MMP-2) and vascular endothelial growth factor (VEGF) expression and on retinal angiogenesis.
Methods:
In this study, the effect of COX-2 or iNOS inhibition on retinal angiogenesis was examined by histopathology. Expression of iNOS, COX-2, MMP-2, and VEGF in the retinas of experimental animals was analyzed using immunohistochemistry, real-time PCR, and Western blotting technologies.
Results:
Inhibition of COX-2 or iNOS attenuated retinal neovascularization and decreased VEGF and MMP-2 expression. An interaction was found between COX-2 and iNOS expression: the iNOS inhibition decreased COX-2 expression and vice versa.
Conclusions:
Our data showed a prominent role of COX-2 and iNOS in hypoxia-induced retinal angiogenesis. The interaction between COX-2 and iNOS is likely to produce a cooperative effect on retinal angiogenesis. The changes of MMP-2 and VEGF expression may play a role in the process of retinal neovascularization.
Insights
Inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) reduces retinal angiogenesis by decreasing VEGF and MMP-2. These pathways interact, suggesting a cooperative role in neovascularization.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pathology
Background:
- Hypoxia-induced retinal angiogenesis involves upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).
- Investigating the interplay between COX and NOS pathways is crucial for understanding retinal angiogenesis.
Purpose of the Study:
- To evaluate the interaction between COX and NOS pathways.
- To determine the effect of this interaction on matrix metalloproteinases 2 (MMP-2) and vascular endothelial growth factor (VEGF) expression.
- To assess the impact on hypoxia-induced retinal angiogenesis.
Main Methods:
- Histopathology was used to examine the effect of COX-2 or iNOS inhibition on retinal angiogenesis.
- Immunohistochemistry, real-time PCR, and Western blotting analyzed the expression of iNOS, COX-2, MMP-2, and VEGF in experimental retinas.
Main Results:
- Inhibition of COX-2 or iNOS significantly attenuated retinal neovascularization.
- VEGF and MMP-2 expression levels were decreased following COX-2 or iNOS inhibition.
- A reciprocal interaction was observed between COX-2 and iNOS expression, where inhibiting one decreased the expression of the other.
Conclusions:
- COX-2 and iNOS play a significant role in hypoxia-induced retinal angiogenesis.
- The interaction between COX-2 and iNOS likely contributes cooperatively to retinal angiogenesis.
- Modulation of MMP-2 and VEGF expression is implicated in the neovascularization process.

