肿瘤坏死因子α反义寡核苷酸对鼠单疱病毒性视网膜炎的影响

Effect of Antisense Oligonucleotides Targeting TNF-α on Murine HSV-1 Retinitis

目的观察不同部位注射肿瘤坏死因子α(TNF-α)反义寡核苷酸对实验性单疱病毒性视网膜炎的影响。方法BALB/c小鼠右眼前房注射单纯疱疹病毒-1(HSV-1),同时左眼结膜下或玻璃体注射TNF-αASON治疗,观察其组织学变化并测定小鼠眼的TNF-α含量,比较2种治疗方式的效果。结果试验组小鼠眼TNF-α发生视网膜炎的几率及严重度明显减少;玻璃体注射组TNF-α含量更低。结论采用作用于TNF-α的反义寡核苷酸局部治疗小鼠单疱病毒性视网膜炎,能明显降低感染小鼠眼内细胞因子TNF-α的含量,减轻眼内视网膜炎症反应。结膜下注射给药也许是更好的方法。

Objective To investigate the effect of local treatment with antisense oligonucleotides （ASON） targeting tumor necrosis factor-α（TNF-α） at different positions on experimental herpes simplex virus （HSV）-I retinitis. Methods After HSV-1 （KOS）was injected in the right anterior chamber（AC） in BALB/c mice,the left eyes were treated with TNF-α ASON by subconjunctival or vitreous injection,and the course of contralateral retinitis was evaluated. The ocular TNF-ct content was quantified by ELISA. Results In the TNF-ct ASON-treated eyes, TNF-ot expression and the incidence and severity of retinitis were reduced. The effect of different injection sites was uncertain. Conclusion ASON can reduce TNF-αcontent and alleviate the inflammatory reaction. Subconjunctival injection may be better.