改良聚羟乙基丙烯酸甲酯-聚甲基丙烯酸甲酯一体化人工角膜植入兔与猴角膜的研究

目的 探讨聚羟乙基丙烯酸甲酯（PHEMA）海绵支架材料与角膜组织的生物相容性,评价改良PHEMA-聚甲基丙烯酸甲酯（PMMA）一体化人工角膜植入兔与猴角膜的初步临床效果。方法通过两个阶段化学聚合结合车床机械切削合成改良的一体化人工角膜。实验分为两个部分完成。第1部分（A组）：将PHEMA海绵边裙材料植入10只正常兔角膜板层间,术后2、4周及2、3、4个月分别行组织病理、免疫组织化学及电镜检查,观察海绵边裙与角膜组织的生物学愈合情况。第2部分（B组）：8只兔眼和2只猴眼角膜囊袋内Ⅰ期植入一体化人工角膜,术后临床观察材料与组织的愈合情况;术后3个月时行Ⅱ期手术切除术眼角膜中央前板层角膜组织,暴露人工角膜中央镜柱,术后随访时间3—6个月,初步观察临床治疗效果。结果（1）A组：10只兔眼随访期间未见并发症。组织病理学显示,PHEMA海绵边裙材料植入术后2周始有成纤维细胞长入,术后2—3个月时多量成纤维细胞长入并伴有新生血管生长;免疫组织化学显示,海绵孔隙中长入的细胞和角膜基质细胞均对波形蛋白免疫反应呈阳性;电镜下可见,成纤维细胞在海绵材料间隙中生长,细胞生长状态良好,并分泌胶原和细胞外基质。（2）B组：6只兔眼的一体化人工角膜均在位,另2只兔眼Ⅰ期术后有前板层角膜基质融解。2只猴眼于Ⅰ期和Ⅱ期术后均未见明显并发症。结论PHEMA海绵能与角膜组织良好的生物学愈合;改良PHEMA—PMMA一体化人工角膜植入术后能获得相对稳定的治疗效果。（中华眼科杂志．2007,43：602-607）

Implantation of modified polyhydroxyethyl methacrylate-polymethyl methacrylate keratoprostheses in rabbit and monkey corneas

OBJECTIVE: To investigate the biocolonization of polyhydroxyethyl methacrylate (PHEMA) sponge with cornea tissue and evaluate the therapeutic effects of modified porous PHEMA-PMMA (polymethyl methacrylate) Keratoprostheses (KPro) on rabbit and monkey corneas. METHODS: The KPro were made using two-stage polymerization combined with mechanical cutting. The experiment was divided into two groups. In the control group (A group), ten normal rabbit eyes received lamellar implantation of PHEMA sponges. The sponges were obtained 2 weeks, 1, 2, 3 and 4 months after operation. The cell proliferation and neovascularization inside the sponges were observed using light and transmission electron microscopy (TEM) and immunohistochemistry. In the experimental group (B group), the porous PHEMA-PMMA KPros were inserted into the lamellar pockets of ten rabbit corneas and two monkey corneas (stage I operation). The healing process was investigated by slit-lamp microscopy. The anterior lamellar cornea tissues were removed 3 months after surgery, exposing the underneath transparent core (stage II operation). The operated eyes were then followed up for 3 - 6 months. RESULTS: No complication was observed in A group. Under the light microscope, fibroblasts started to grow into the cornea 2 weeks after operation; lots of cells, accompanied with new blood vessels, invaded into the cornea 2 - 3 months after surgery. Invading cells of sponge, as well as keratocyte, were positive for vimentin. Under the electron microscope, the invading cells looked healthy and were surrounded by extracellular matrix and collagen. In B group, eight rabbit eyes which have received KPro implantation, anterior lamellar cornea melting happened in two eyes after the stage I operation. The remaining six corneas retained their central cores during observation after the stage II operation. Two monkey operated eyes were found no complication throughout the whole follow-up. CONCLUSIONS: The PHEMA sponge can obtain a tight fusion with the host cornea. The modified PHEMA-PMMA KPros have obtained a relatively stable therapeutic results after implantation into animal corneas.