In hypoxia-induced extraretinal neovascularization, other angiogenic factors are also involved in the development of neovascularization. Some reports have suggested an interaction between the expression of these angiogenic factors and the expression of MMPs.
16 17 18 19 Therefore, to examine the possibility that the observed difference in the angiogenic response between wild-type and MMP-2
−/− mice was due to modification of other angiogenesis factors, we investigated VEGF (a potent angiogenic factor) and PEDF (a potent antiangiogenic factor in the eye) expression in hyperoxia-treated wild-type and MMP-2
−/− mice. The results of a typical immunohistochemical analysis are shown in
Figures 4 and 5 . VEGF and PEDF protein expression was consistent with their characteristics as hypoxia-regulated angiogenic and antiangiogenic factors, respectively. At P12, there was VEGF protein expression in the ganglion cell layer and in the inner nuclear layer in room-air–raised wild-type and MMP-2
−/− mice
(Figs. 4A 4B) . The VEGF protein expression in oxygen-incubated P12 wild-type and MMP-2
−/− mice was reduced compared with the age-matched control
(Figs. 4C 4D) . At P17, VEGF expression increased in oxygen-incubated wild-type and MMP-2
−/− mice
(Figs. 4H 4I) , and there were higher VEGF levels than in age-matched room-air–raised P17 mice
(Figs. 4F 4G) . There was no difference in VEGF expression between wild-type and MMP-2
−/− mice from P12 to P17. At P12, there was faint PEDF protein expression in Müller glial cell process and in the ganglion cell layer in room-air–raised wild-type and MMP-2
−/− mice
(Figs. 5A 5B) . The PEDF protein expression in oxygen-incubated P12 wild-type and MMP-2
−/− mice increased compared with that in the age-matched control
(Figs. 5C 5D) . At P17, the PEDF protein levels decreased in oxygen-incubated wild-type and MMP-2
−/− mice, and the levels were lower than that of age-matched room-air–raised P17 mice
(Fig. 5F 5G 5H 5I) . Also, there was no difference in PEDF expression between wild-type and MMP-2
−/− mice throughout this period.