雷帕霉素修饰人工晶状体植入兔眼后表面黏附细胞的实验研究

Experimental study on adhesion cells at surface of rapamycin modified intraocular lens after implantation in rabbit

目的将雷帕霉素修饰人工晶状体(intraocular lens,IOLs)植入兔眼内,观察IOLs表面黏附细胞的状况,评价雷帕霉素修饰IOLs的生物相容性。方法将雷帕霉素与体积分数1%高分子多聚乳酸/多聚羟基乙酸混悬液通过静电喷涂沉积设备喷涂于IOLs光学区的外周(直径范围在4mm以外区域),制备出雷帕霉素修饰的IOLs。兔眼行透明晶状体超声乳化吸出,植入不同的IOLs并分为3组:A组(雷帕霉素修饰IOLs组,RAPA组)、B组(单纯涂层组,高分子多聚乳酸/多聚羟基乙酸组)、C组(空白对照组,普通PMMAI OLs组),每组各10只。术后3个月将兔处死,摘出眼球,取出IOLs并固定于多聚甲醛溶液中,HE染色后,对IOLs黏附的细胞情况进行分析。结果涂层雷帕霉素药物颗粒细小,均匀分布于IOLs表面。低倍镜下观察,A组IOLs表面细胞分布稀疏,B组和C组细胞密集,且细胞分布均匀;A组IOLs表面的细胞平均数量为26.56±6.10,B组为83.60±13.38,C组为79.33±9.46。经SPSS 13.0统计学软件检验,A组与B组、C组相比差异有显著统计学意义(P=0.000),而B组和C组表面的细胞数量差异无统计学意义(P>0.05)。高倍镜下观察IOLs表面细胞种类,主要有小圆细胞、纤维样细胞、巨噬细胞、异物巨细胞、上皮样细胞。A组中小圆细胞所占比例为53.3%,B组为45.0%,C组为37.8%。A组中巨噬细胞所占比例为20.0%,B组为15.0%,C组为22.6%。结论高分子可降解材料联合雷帕霉素修饰的IOLs具有良好的生物相容性。

Objective To evaluate the biocompatibility of intraocular lens （IOLs） modified by rapamycin through implanting into rabbits eyes and observe the adhesion cells on the surface of IOLs.Methods The suspension of rapamycin and 1% poly lactic-coglycolic acid（PLGA） were used as sprayed coating at the periphery of IOLs （out of the diameter of 4 mm） by static spray-coating instruments to made rapamycin modified IOLs.After transparent lens were removed by phacoemulsification,different IOLs were implanted into rabbits eyes and divided into 3 groups：Group A （RAPA group）,IOLs modified by rapamycin;Group B（PLGA group）,IOLs sprayed only by PLGA;Group C（control group）,normal PMMA IOLs without any treatment,10 rabbits in each group.After all rabbits were ethically killed,IOLs were fixed in formaldehyde solution after taken out.The cells on the surface of IOLs were analyzed by light microscope after HE staining.Results Sprayed coating of rapamycin were with small particles and equally distributed on IOLs.Under low power microscope,the cell distribution of group A was sparse on the surface of IOLs,while was intensive and equally distributed in group B and C;The cell number on surface of IOLs were 26.56±6.10,83.60±13.38 and 79.33±9.46 in group A,B and C,respectively.There were statistically significant differences between group A and B or C（P=0.000）.No significant difference of cell number was found between group B and C（P〉0.05） by LSD-t test of SPSS 13.0.Under high power microscope,the varieties of cells on IOLs were mainly small round cells,fibroblast-like cells,macrophage,foreign-body giant cells and epithelioid cells.The proportion of small round cells in A,B,C groups were 53.3%,45.0%,37.8%,respectively;Macrophage were 20.0%,15.0%,22.6%,respectively.Conclusion The IOLs modified by the compound of high molecule material PLGA and rapamycin shows good biocompatibility.