慢性高眼压SD大鼠视网膜小胶质细胞CD11b表达研究

目的 探讨慢性高眼压SD大鼠在不同眼压下视网膜小胶质细胞CD11b表达情况及视网膜损害程度与小胶质细胞功能的相关性.方法 实验研究.采用532-激光建立SD大鼠慢性高眼压模型,对大鼠前房角进行90～110个点的光凝固,分别在光凝后2周、1…2 3 5及6个月测量大鼠眼压,在相应的时间点,以免疫组织化学方法检测大鼠视网膜小胶质细胞膜表面抗原CD11b表达阳性率.四甲基葡聚糖罗丹明标记视网膜神经节细胞(RGC)并计数.应用SPSS 13.0统计学软件进行数据处理,采用组间对比t检验,比较对照组与实验组不同时间点的眼压值.回归分析判断眼压升高率与RGC损失率及小胶质细胞CD11b表达阳性率的相关性.结果 造模后2周,实验组SD大鼠眼压开始升高,但与对照组相比差异无统计学意义(t=1.124,P=0.287);1个月时实验组眼压升高达到峰值为(24.156±2.704)mm(1 mmHg=0.133 kPa),与对照组(15.930±3.278)mm Hg比较,差异有统计学意义(t=2.487,P=0.036);其后眼压逐渐下降,6个月时眼压恢复至对照组水平(t=1.103,P=0.290).造模后2周,实验组视网膜小胶质细胞CD11b表达阳性;1个月时,CD11b表达阳性细胞明显增多,与对照组相比差异有统计学意义(t=3.333,P=0.008);1个月后,小胶质细胞表达CD11b仅限于视网膜内丛状层和内颗粒层;CD11b表达水平与眼压的升高峰值时间一致(r=0.891,P=0.014).实验组RGC呈持续性损害,至6个月时,RGC数量降至最低值,与对照组比较差异有统计学意义(t=2.316,P=0.045).RGC密度下降率与眼压升高率呈显著相关性(r=0.757,P=0.021).结论 慢性高眼压SD大鼠在造模后不同时段视网膜小胶质细胞CD11b表达水平与眼压升高程度具有明显的相关性,提示小胶质细胞有可能在眼压导致的损伤中发挥呈递损伤抗原作用,从而导致自体抗原产生,启动免疫过程.

Expression of CD11b in the retinal microglia in chronic hypertension rat

Objective To study the expression of CDllb in the retinal microglia in laser induced ocular hypertension (OHT) SD rat. Methods It was an experimental study. OHT was induced by the coagulation of trabecular meshwork using 532-laser in sixty SD rats. Intraocular pressure (lOP) was measured by Tonopen-XL, the expression of CDI I b in retinal microglia detected by immunohistochemistry, and retinal ganglion cells (RGCs) were labeled with Dextran Tetramethyl Rhodamine (DTR) and counted by Image-Pro Plus Version 6.0 image analysis software at 2 weeks, 1, 2, 3, 4, 5, and 6 months, respectively. All the numerical data were statistically analyzed by SPSS 13.0 software. Results Although the lOP of experimental groups are still the similar level at 2w after coagulation (t = 1.124, P = 0.287),Compared to control eyes, IOP in lasered eyes was significantly (t = 2.487, P = 0.036) increased at 1 month, lasting for3 months and returned to normal from 5 to 6 months(t = 1.103,P =0.290). The expression of CD11 b in the retinal microglia in the lasered eyes was significantly more intensive than that in control eyes at 1 month (t = 3.333, P = 0.008) and faded after 5 months, a similar pattern to IOP response, that two group data shows significant dependability (r = 0.891, P = 0.014). The number of RGC was significantly reduced from 1 month to 6 months (t = 3.316, P = 0.009), the velocity of reducing seems dependability to the advancing ofIOP (r=0.757,P=0.021). Conclusions The expression of Cdiib in retinal microglia is fluctuated with chronic OHT pattern and RGCs injury level indicating that the injury antigens by microglia are presented in the retina with the increase of IOP and activate the immunologic process leading to glaucomatous RGCs damage. It suggests that it is important to effectively control the IOP in order to reduce the risk of immune induced retinal damage by microglia.