Interaction between iNOS and COX-2 in hypoxia-induced retinal neovascularization in mice.
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.
He
Tao
T
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.
Xing
Yi-Qiao
YQ
Zhao
Xiao-Hui
XH
Ai
Ming
M
D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D015861:Retinal Neovascularization / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2