Objective   To study the effect of eicosapentaenoic acid (EPA) on expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1 in corneal neovascularization (CNV) of rats and its mechanism of action.  Methods   Seventyeight SprayueDawley rats were randomly divided into group A treated with 0.02 mg EPA (n=24)

group B treated with 0.03 mg EPA (n=24)

group C (control group

n=24)

and group D (normal group

n=6). A model of right eye injury was induced by alkali cauterization. A solution containing 0.02 mg/0.04 ml and 0.03 mg/0.04 ml of EPA and 0.04 ml of saline was injected subconjunctivally in groups A

B and C immediately after alkali cauterization. CNV and corneal edema were observed daily under a slitlamp biomicroscope. On days 1

4

7 and 14 after operation

vascular endothelial cells were stained with CD34 using immunohistochemical method. VEGF mRNA and Flk-1protein expressions were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis.  Results    The relative area of CNV in groups A and C was 15.80%±6.43% and 11.06%±2.14%

16.10%±7.41% and 11.06%±2.51%

84.74%±7.77% and 89.63%±7.50%

respectively

in 7 and 14 d after injury induced by alkali cauterization. The relative area of CNV was significantly lower in groups A and B than in control group in 7 and 14 d after injury induced by alkali cauterization (P0.05). The vascular endothelial cells in corneal stroma of group C were strongly stained with CD34 and the endothelial marker was negatively stained in EPA-treated avascular stroma. The VEGF mRNA and Flk-1 protein expression levels were the highest in groups C in 1 and 4 d after injury induced by alkali cauterization

and then decreased

and were significantly lower in groups A and B than in control group in 4 d after injury induced by alkali cauterization (P0.05).  Conclusion   Topical application of EPA can inhibit the expression of VEGF and its receptor Flk-1 through the VEGF pathway

thus significantly suppressing CNV.