AIM: To study the regulation mechanism of diet containing omega-3 polyunsaturated fatty acids(ω-3 PUFAs)on retinal neovascularization in an oxygen-induced retinopathy(OIR)mouse model.

METHODS: Sixty C57BL /6J mice, seven-day-old, were classified into 3 groups: A the normal control group, B the OIR model group, C the ω-3 PUFAs diet group. Each group has twenty mice and separated fed by their lactating mice. The normal control group was fed in a standard atmosphere environment, B, C groups were first fed in a hyper-oxygen atmosphere of(75±2)% oxygen percentage for 5d, then continue fed in a standard atmosphere. The ω-3 PUFAs diet group was fed with dose base on their weight by 7.5mg/kg/d. All mice were sacrificed when they were seventeen-day-old, the relative neovascularization areas(NA)were calculated by fluorescein angiography on flat-mounted retina. The number of endothelial cell nuclei breaking through the inner linmiting membrane(ILM)was counted on hematoxylin and eosin-stained retinal section. The ω-3PUFAs/ω-6PUFAs relative amount and ratio was measured by GC-MS in the retina. A real-time PCR and Western Blot method were used to detect the mRNA, peroxisome proliferator-avtivated receptor–γ(RPAR-γ), vascular endothelial growth factor-A(VEGF-A)and vascular endothelial growth factor receptor 2(VEGFR-2)in the retina.

RESULTS: There was a significant different in all groups on the relative neovascularization areas and the number of endothelial cell nuclei breaking through the ILM(F_NA=20.45, P<0.05; F_ILM=48.66, P<0.05). NA between Group A and B had a significant difference(t=8.64, P<0.05), the same between Group C and B(t=8.91, P<0.05). The cell nuclei breaking through ILM in Group A and B was significantly different(t=38.51, P<0.05), the same in Group C and B(t=19.86, P<0.05). For the relative contain in retina of ω-3PUFAs and ω-6PUFAs, there was a significant different among all groups(F=129.86, F=112.44; all P<0.05). That of Group C was significant different than other two groups(t=23.15, 25.42; t=16.43, 11.95; P<0.05). There were significant different among all groups on ω-3PUFAs/ω-6PUFAs ratio, retinal RPAR-γmRNA expression, retinal VEGF-A mRNA expression and VEGFR-2 mRNA expression(F_ω-3/6=10.30, F_RPAR-γ=138.24, F_VEGF-A=69.12, F_VEGFR-2=52.45; P<0.05). The ω-3PUFAs/ω-6PUFAs ratio of Group C was higher than that of Group B(P<0.05). Compared to Group B, on one hand Group C had a higher expression(P<0.05), on other hand Group C had a lower expression on VEGF-A mRNA and VEGFR-2 mRNA(P<0.05).

CONCLUSION:The diet rich with ω-3 PUFAs uplifts the ω-3PUFAs/ω-6PUFAs ratio and activates RPAR-γ to lower expression of VEGF-A and VEGFR-2 to inhabit oxygen induced retinal neovascularization.