国产亲水性丙烯酸人工晶状体的生物相容性研究

发布时间：2019-01-20 18:36

【摘要】： 目的：软性人工晶状体(Intraocular Lens IOL)是目前白内障术中使用的主流人工晶状体,而我国软性IOL的研发尚处于起步阶段。本研究拟对天津泰达生物科技有限公司研发的软性亲水性丙烯酸IOL进行体外的细胞毒性检测,并将其植入兔眼内以综合评价其生物相容性。方法：分为体外和体内实验两部分。 1.体外,选择亲水性丙烯酸、疏水性丙烯酸和硅凝胶三种软性材料的IOL进行生物相容性和细胞毒性的观察和比较。分别提取人外周血的血小板、中性粒细胞,小鼠腹腔巨噬细胞、人眼结膜囊成纤维细胞置于三种IOL表面并培养,观察其细胞粘附生长的数量与状态。 2.选择表皮葡萄球菌标准菌株对以上三种软性IOL及聚甲基丙烯酸甲酯(polymethyl methacrylate PMMA)IOL、肝素修饰PMMA IOL进行细菌粘附的比较。 3.体内,依照国家标准和国家医药局发布的《眼内IOL》标准,选择已临床应用的进口亲水性丙烯酸IOL作为对照IOL,进行家兔眼内植入的初步研究。选择日本大耳白兔26只,分为4组：第一组为正常对照,2只兔,第二组16只兔,行双眼超声乳化晶状体吸除后,一眼植入实验IOL,另一眼植入对照IOL；第三组4只兔,晶状体乳化吸除后一眼植入实验IOL,一眼不植IOL；第四组4只眼,晶状体乳化吸除后一眼植入对照IOL,另一眼不植入IOL,共计各有20枚实验和对照IOL植入兔眼内。 4.分别于术后1周、1月、3月抽取兔眼前房水进行白细胞计数,并行裂隙灯检察,观测眼前节的反应。于术后1月、3月分别处死第二组的5只兔,取出IOL进行扫描电镜检查,并在同时期各处死第三、四组的2只兔,摘除眼球,行兔眼前、后节的病理观察。结果： 1.体外,血小板和中性粒细胞在亲水性丙烯酸IOL表面粘附的最少,明显少于疏水性丙烯酸和硅凝胶IOL；小鼠腹腔巨噬细胞在亲水性丙烯酸IOL表面的粘附少于疏水性丙烯酸IOL,而与硅凝胶IOL无显著性差异；人结膜囊成纤维细胞在疏水性丙烯酸IOL表面生长最密集,亲水性丙烯酸IOL表面的成纤维细胞粘附的较少,但形态健康。 2.表皮葡萄球菌在亲水性丙烯酸IOL上粘附的最少,与肝素修饰的IOL相当,在硅凝胶IOL表面粘附的最多。 3.兔眼内,实验国产亲水性丙烯酸IOL植入术后7天,房水白细胞计数较对照组多,其余各观察时间(30天、90天)的房水白细胞计数两组间无显著性差异。国产亲水性丙烯酸IOL植入后角膜水肿、前房渗出及IOL表面附着物情况的裂隙灯检查,与进口亲水性丙烯酸IOL相比均未见明显区别。 4.IOL取出后扫描电镜显示,术后1个月,国产亲水性丙烯酸IOL表面可见少量蛋白膜,巨噬细胞成团分布,术后3个月,表面蛋白膜缩小,巨噬细胞单个分布,与进口对照组之间无显著性区别。 5.兔眼摘除后,两组眼前节组织病理学检查均表现为：术后1个月,前房内少量渗出物,房角开放,术后3个月,渗出吸收,房角仍大部分开放,视网膜组织各层结构大致正常。结论： 1.国产亲水性丙烯酸IOL在体外表现为较低的细胞粘附和细菌粘附,无细胞毒性。 2.兔眼内,国产亲水性丙烯酸IOL与进口对照IOL相比,同样具有良好的葡萄膜相容性和较好的囊膜相容性。
[Abstract]:Purpose: The soft intraocular lens (IOL) is the mainstream intraocular lens used in the current cataract operation, and the development of the soft IOL in China is still in the beginning In this study, the soft hydrophilic acrylic IOL developed by Tianjin Taida Biotech Co., Ltd. was tested for cytotoxicity in vitro, and it was implanted in rabbit eyes to evaluate its biological activity. Compatibility. Method: minutes in vitro and in vivo, two parts of soft materials of hydrophilic acrylic acid, hydrophobic acrylic acid and silicon gel are selected to be produced, The human peripheral blood platelet, the neutrophils, the mouse peritoneal macrophages and the human conjunctival sac fibroblasts are respectively extracted to the surface of the three IOLs and cultured, the number and the status of the cell adhesion growth were observed. A comparison of the bacterial adhesion of the prime-modified PMMA IOL. In vivo, the clinically applied imported hydrophilic acrylic acid I was selected in accordance with the National Standards and the <-eye IOL> criteria issued by the National Institute of Medicine. OOL was used as a control IOL for the initial study of the in-eye implantation of rabbit. 26 rabbits were selected as normal control, 2 rabbits and 16 rabbits in the second group. After the two eyes of the two eyes were absorbed and removed, the experimental IOL was implanted at one glance and the control IOL was implanted at another glance; and Four rabbits were implanted in three groups, the lens was emulsified and the IOL was implanted at a glance, and the IOL was not implanted at a glance; the fourth group was 4 eyes, the lens was emulsified and the control IOL was implanted at a glance, and the other one was not implanted A total of 20 experimental and control IOLs were implanted in the rabbit eye. 4. The rabbit eyes were extracted 1 week, 1 month and 3 months after the operation, respectively. White blood cell count and parallel slit lamp were performed in the anterior chamber to observe the reaction of the anterior segment. In January and March of the operation, 5 rabbits of the second group were sacrificed, and the IOL was taken out for scanning electron microscope and the patients were sacrificed at the same time. third, The results were as follows: 1. In vitro, the adhesion of platelets and neutrophils to the surface of the hydrophilic acrylic IOL was the least, significantly less than that of the hydrophobic acrylic and silicone IOLs.; the adhesion of the mouse peritoneal macrophages to the surface of the hydrophilic acrylic IOL was less than that of the hydrophobic acrylic IOL and no significant difference with the silicone IOLs; the human conjunctival sac fibroblasts were in the hydrophobic acrylic IOL table the surface growth was the most dense, the surface of the hydrophilic acrylic IOL had less adhesion, but the morphology was healthy. The minimum amount of adhesion to the acrylic IOL, comparable to the heparin-modified IOL, was the most adhesive on the surface of the silicone IOL. 3. In the rabbit eye, 7 days after the implantation of the home-made hydrophilic acrylic IOL, the aqueous white There was no significant difference between the two groups in the control group, and the remaining observation time (30 days, 90 days) showed no significant difference between the two groups. The domestic hydrophilic acrylic IOL was implanted with corneal edema. The examination of the slit lamp of the exudation of the anterior chamber and the attachment of the surface of the IOL was not significantly different from that of the imported hydrophilic acrylic IOL. 4. The scanning electron microscope showed that the surface of the domestic hydrophilic acrylic IOL could be seen with a small amount of protein film after the operation for 1 month after the IOL was taken out. and after 3 months of operation, the surface protein membrane was reduced, the single distribution of the macrophages, and no significant difference between the control group and the control group. 1 month There was a small amount of exudate in the front room, the angle of the room was open, 3 months after the operation, the effusion was absorbed, the angle of the room was still largely open, and the retina The structure of each layer of the tissue is generally normal. Conclusion: 1. The domestic hydrophilic acrylic IOL is shown to be low in cell adhesion and bacteria in vitro.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R779.66

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