睫状神经营养因子玻璃体内注射对青光眼视神经保护作用的实验研究

Neurprotective function of CNTF intravitreal injection in the model of glaucoma

目的探讨睫状神经营养因子（CNTF）玻璃体内注射对鼠慢性青光眼视神经的保护作用。方法通过散瞳、前房穿刺放液及角膜缘激光光凝等步骤制造鼠慢性青光眼模型。设正常对照组、前房穿刺对照组、未治疗组（仅造模）、治疗组（造模后双眼玻璃体内注入CNTF）、治疗对照组（造模后双眼玻璃体内注入生理盐水）。观察视网膜组织磷酸化信号转导与转录激活子3（pSTAT3）表达、视神经轴突及闪光视觉诱发电位（F-VEP）变化。结果正常状态pSTA33在视网膜组织中极少表达，眼压升高后1d开始上升，2d达到高峰，14d下降到正常水平。治疗组视网膜中pSTAT3在眼压升高14d和28d表达均高于同时间段的未治疗组及治疗对照组（P〈0．05）。在眼压升高28d治疗组视神经纤维阳性面积比率的值明显高于未治疗组及治疗对照组，且VEPP，波潜伏期明显低于以上两组（P〈0．05）。结论CNTF玻璃体内注射延缓了鼠慢性青光眼视神经的损伤。眼压升高初期，视网膜STAT3信号传导途径暂时被激活，CNTF相对长时间激活了STAT3信号传导途径，STAT3信号传导途径参与介导了CNTF对视神经的保护作用。

Objective To investigate the neuroprotective function of ciliary neurotrophic factor （CNTF） intravitreal injection in the model of chronic glaucoma in rats. Methods SD rats were used to de velop chronic glaucoma model. First, pupil dilation;Second, the anterior chamber was flattened by aspiration of aqueous humor;Third, laser photocoagulation was performed to the limbus. Groups：Normal control group, Aterior chamber flattened group, Non treatment group、 Treatment group （ CNTF intravitreal injection ） , Treat ment control group（O. 9% sodium chloride injection intravitreal injection）. Expression of phosphorylated sig nal transducer and activator of transcription（ sSTAT3 ） in the retinal tissue ,optic nerve axons and flash visual evoked potential （F VEP） in different periods were observed. Results There was little expression of pSTAT3 in the normal retina. The expression of sSTAT3 increased in the first day of IOP being elevated in the non treatment group,which reached its maximum in the second day and dropped to normal levels in the 14th day. In the CNTF treatment group,the expression of pSTAT3 was still higher in the 14th and 28th day of IOP being elevated than that in the non treat ment group and treatment control group. At the end of this study （ 28 d） the rate of positive area of optic nerve fibre in the treatment group was significantly higher than that inthe non treatment group and treatment control group （P 〈 0.05 ）. The latency time of F VEP in the non treat ment group was significantly prolonged,which was longer than that in the treatment group（P 〈 0.05 ）. Con clusion CNTF intravitreal injection has protective effect on the retinal tissue in the model of chronic glauco ma in rats, which relieves the trauma of optic nerve. During the early stage of chronic glaucoma, STA33 path way was activated temporarily. CNTF induced the comparatively long period activated of STAT3 pathway. STAT3 pathway , as one of the signal pathways of CNTF, took part in the the neuroprotective function of CNTF.