METHODS: A total of 160 postnatal day(P)7 C57BL/6 mice were obtained. All mice except normal control group were exposed to(75±2)% oxygen environment for 5d and then kept in room air for another 5d to establish the OIR mice model. All mice in normal control group(40 mice)were exposed to room air only. At P12 and P14, respectively, mice in PEDF treatment group were injected intravitreously with recombinant human PEDF(2μg/eye,1μL)in the right eye, while mice in treatment control group were injected intravitreously with the same volume of vehicle [1μL, 10mmol/L phosphate buffered saline(PH7.4), PBS] in the right eye. All mice were euthanized at P17. Eyes were whole mounted and stained with Lectin to observe the growth of abnormal RNV; And retinal specimens were prepared for PEDF, MCP-1 protein and mRNA analysis by Western blot and real time RT-PCR respectively.

RESULTS: Changes of retinal vessels had been detected by fluorescence microscopy on flat-mounted retina. The relative RNV areas were significantly increased in OIR model group compared with those in normal control group(P<0.01). However, the relative RNV areas were significantly reduced in PEDF treatment group compared with those in PBS treatment control group(P<0.01). The specific expression of MCP-1 protein and mRNA in the OIR model group were higher than those of normal control group, presenting a statistically significance(both P<0.05). The specific expression of PEDF protein and mRNA in the OIR model group showed a considerable decline in comparison with normal control group, presenting a statistically significance(both P<0.01). And the specific expression of MCP-1 protein and mRNA in those of PEDF-treated group showed a considerable decline in comparison with PBS-treated group, and the differences were statistically significant(both P<0.05). However, there were increase of the expression of MCP-1 protein and mRNA between normal control group and PEDF-treated group, presenting no statistically significance(both P>0.05).

CONCLUSION: PEDF could inhibit oxygen-induced retinal neovascularization and down-regulate retinal MCP-1 expression under hypoxia, which may underlie its anti-neovascularization effects and play a role of protection in ischemic retinopathy.