Georgiou Tassos, Wen Yao-Tseng, Chang Chung-Hsing, Kolovos Panagiotis, Kalogerou Maria, Prokopiou Ekatherine, Neokleous Anastasia, Huang Chin-Te, Tsai Rong-Kung
Ophthalmos Research and Educational Institute, Nicosia, Cyprus.
Institute of Eye Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1603-1611. doi: 10.1167/iovs.16-20979.
The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION).
The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects.
Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group.
The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.
本研究旨在探讨ω-3多不饱和脂肪酸(ω-3 PUFA)给药对大鼠前部缺血性视神经病变(rAION)模型的治疗效果。
测量血液中花生四烯酸/二十碳五烯酸(AA/EPA)水平以确定建议剂量。对诱导出rAION的大鼠连续10天每日经口灌胃给予鱼油(1克/天EPA)或磷酸盐缓冲盐水(PBS),以评估神经保护作用。
血液脂肪酸分析显示,鱼油治疗10天后,AA/EPA比值从17.6降至≤1.5。与PBS治疗组相比,ω-3 PUFA治疗组的视网膜神经节细胞(RGC)密度和闪光视觉诱发电位(FVEP)的P1-N2波幅显著更高(P<0.05)。与PBS治疗的大鼠相比,ω-3 PUFA治疗的大鼠RGC层中的凋亡细胞数量显著减少(P<0.05)。在rAION模型中,ω-3 PUFAs治疗使视神经(ON)处的巨噬细胞募集减少了3.17倍。与PBS治疗组相比,ω-3 PUFA治疗组诱导产生了减少炎症的M2巨噬细胞标志物。此外,ω-3 PUFA治疗组中肿瘤坏死因子-α、白细胞介素-1β和诱导型一氧化氮合酶的mRNA水平显著降低。
给予ω-3 PUFAs对rAION具有神经保护作用,可能是通过RGC抗凋亡和减少炎症细胞浸润的抗炎双重作用,以及调节巨噬细胞极化以减少细胞因子诱导的视神经损伤来实现的。