大鼠慢性高眼压模型视网膜神经节细胞谷氨酸受体2表达的研究

Expression of glutamate receptor 2 in retinal ganglion cells in the eyes with chronic elevated intraocular pressure:experiment with rats

目的探讨青光眼视网膜神经节细胞(RGC)选择性损伤机制。方法用结扎上巩膜静脉联合术后球结膜下注射5-氟尿嘧啶的方法建立大鼠慢性高眼压模型。模型建立后1周、1个月,在视网膜铺片上行免疫组织化学染色,在激光共聚焦显微镜下观察视网膜谷氨酸受体(GluR)2以及神经丝蛋白(NF)-68的表达情况。结果结扎上巩膜静脉联合术后球结膜下注射5-氟尿嘧啶可诱导较长时间稳定高眼压,1个月内12只高眼压眼眼压均大于22 mm Hg(1 mm Hg=0.133 kPa)。在正常对照组及高眼压组,大、中、小直径的 RGC 均可表达 NF-68,但 NF-68在大直径的神经节细胞的表达更为明显。在正常对照组,大鼠大 RGC 均缺乏 GluR2的表达,而中、小直径 RGC 大都可表达 GluR2;高眼压1周以及1个月组,中、小直径 RGC GluR2的表达没有明显变化;高眼压1周,NF-68阳性的大直径的 RGC 仍缺乏 GluR2的表达;但到高眼压1个月,残存 NF-68阳性的大直径的 RGC 开始表达GluR2。结论大 RGC 对高眼压的易损性可能与其特异性缺乏 GluR2表达有关。

Objective To investigate the mechanism of selective damage of retinal ganglion cells （RGCs） in glaucoma. Methods （ 1 ） The right eyes of 12 SD rats underwent ligation of 2 episcleral veins and subconjunctival injection 5-fluoro-uracilum so as to establish chronic elevated intraocular pressure glaucoma rat model. Six SD rats were used as controls. Intraocular pressure （IOP） was measured every week. （2） One week and 4 weeks after the operation 6 glaucoma rats and 3 control rats were killed with their eyes taken out to undergo immuno-histological assays to observe the expression of glutamate receptor （GluR）-2 and neurofilament （NF）-68 in the RGCs with different sizes by confocal laser scanning microscope. Results （ 1 ） The IOP was increased since 1 week after the operation. The elevated IOP was consistently maintained for up to 4 weeks in the glaucoma group. （2） All the RGCs of both groups were NF- 68 positive, especially the larger RGCs. （3） GluR2 was not expressed in the larger RGCs of both the glaucoma and control groups, and was expressed in the small and intermediate RGCs of the glaucoma group up to the end of experiment. However, 4 weeks after the operation the residual NF-68 positive larger RGCs of the glaucoma group showed GluR-2 expression. Conclusion The vulnerability of the RGCs may be related to the specific deficiency of GluR-2 expression.