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.
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.
Authors: S Priya Narayanan; Modesto Rojas; Jutamas Suwanpradid; Haroldo A Toque; R William Caldwell; Ruth B Caldwell Journal: Prog Retin Eye Res Date: 2013-07-03 Impact factor: 21.198