山茱萸总甙滴眼液防治角膜移植免疫排斥反应的实验研究

目的：观察山茱萸总甙（COG)滴眼液局部应用对角膜移植免疫排斥反应的影响。方法：建立封闭群大鼠角膜移植模型，随机分组：A、B、C、D组为Wister—SD组问同种异体角膜移植，Wistar为受体，SD为供体，其中A组为空白对照组、B组为0．5％COG滴眼液组、C组为1％COG滴眼液组，D组为2％COG滴眼液组，E组为Wistar—Wistar对照组，即Wistar大鼠间同种异体移植组。用裂隙灯显微镜记录及比较各组：角膜植片透明度、水肿度、新生血管度、移植排斥指数(RI)及角膜排斥发生时间。结果：术后各组移植排斥指数及发生角膜移植排斥时间，A组与B组、A组与C组、A组与D组、B组与C组、C组与D组比较均有显著性差异，P＜0．01；B组与D组之间比较P＞0．05，无显著性差异。结论：COG滴眼液能有效地防治角膜移植免疫排斥反应，1％COG滴眼液更有效。     

雷公藤多甙防治角膜移植免疫排斥反应的实验研究

用兔同种异体角膜移植模型，观察了雷公藤多甙及联合环孢霉素A对植片存活时间和移植抗原诱导的迟发型超敏反应的影响。结果显示：与对照组相比，雷公藤多甙组、环孢霉素组和两种药物联合组植片存活时间显著延长，移植抗原诱导的迟发型超敏反应也显著受到抑制；其中联合组的作用又大于两种药物单独应用组。结果提示：雷公藤多甙具有显著延长角膜移植存活和防止免疫排斥反应发生的作用；与环胞霉素A具有一定的协同作用，为进一步应用于临床提供了实验依据。     

雷公藤多甙滴眼液防治角膜移植免疫排斥反应的实验研究

目的观察雷公藤多甙(TⅡ)滴眼液局部应用对角膜移植免疫排斥反应的影响.方法建立大鼠角膜移植模型,随机分组A,B,C组为SD大鼠-Wistar大鼠组间同种异体角膜移植,SD大鼠为受体,Wistar大鼠为供体,其中A组为空白对照组、B组为0.02%TⅡ滴眼液组、C组为0.03%TⅡ滴眼液组,另设D组为SD大鼠同种间对照组、E组为SD大鼠自体对照组.用裂隙灯显微镜记录及比较各组移植排斥指数(RI),包括角膜植片透明度、水肿度、新生血管程度,并比较角膜排斥发生时间.结果术后各组移植排斥指数及发生角膜移植排斥时间,A组与B组、A组与C组、B组与C组比较均有显著性差异,P＜0.05;D组和E组两对照组之间比较P＞0.05,无显著性差异.结论TⅡ滴眼液可有效地防治角膜移植免疫排斥反应,0.03%比0.02%TⅡ滴眼液更有效.     

雷公藤内酯醇滴眼液防治角膜移植免疫排斥反应的实验研究

目的探讨雷公藤内酯醇(T10)滴眼液局部应用对角膜移植免疫排斥反应的影响.方法建立封闭群大鼠角膜移植模型,随机分组A、B、C组为SD-Wistar组间同种异体角膜移植,SD为受体,Wistar为供体,其中A组为空白对照组,B组为o.5mg@L1T10滴眼液组,C组为1mg@L-1T10滴眼液组,D组为SD-SD对照组,即SD大鼠间同种异体移植组和E组SD自体角膜移植对照组.用裂隙灯显微镜记录及比较各组角膜透明度、水肿度、新生血管度、移植排斥指数(RI)以及角膜排斥发生时间.结果术后各组角膜植片透明度、水肿度、新生血管程度以及发生角膜移植排斥时间,A组与C组比较有显著性差异(P＜0.05);D组和E组比较无显著性差异(P＞0.05).结论T10滴眼液可有效防治角膜移植免疫排斥反应.     

转化生长因子-β1对角膜上皮移植排斥反应的影响

为研究ＴＧＦ－β１对角膜上皮所致的外周淋巴细胞亚群ＣＤ４及ＣＤ８活化的影响。我们采用ＣＤ４、ＣＤ８免疫荧光标记及流式细胞仪检测技术,对ＢＡＬＢ／ｃ小鼠角膜上皮移植术后１２ｄ的外周血中ＣＤ４＾＋、ＣＤ８＾＋的表达进行分析。结果发现ＢＡＬＢ／ｃ小鼠角膜上皮移植术后１２ｄ的外周血中ＣＤ４＾＋、ＣＤ８＾＋的表达均有显著升高;术后经ＴＧＦ－β１治疗,ＣＤ４＾＋、ＣＤ８＾＋以及ＣＤ４＾＋／ＣＤ８＾＋明显受到抑     

FK506抑制兔同种异体角膜缘移植免疫排斥反应的实验研究

目的 探讨FK506滴眼液对同种异体角膜缘移植术后排斥反应的免疫抑制作用。方法 新西兰兔48只48眼建立角膜缘缺陷症动物模型。随机分为FK506组、环孢霉素A组及生理盐水对照组3组，每组16眼。1个月后实施同种异体角膜缘移植术，眼表观察10周。结果 术后10周，对照组、环孢霉素A组、FK506组角膜新生血管指数平均秩分别为15．50、8．00、5．00。对照组角膜新生血管指数较其他2组高（P＝0．00）；而FK506组与环孢霉素A组间无显著差异（P＝0．12）；对照组上皮排斥反应发生最早，环孢霉素A组次之，FK506组最晚；术后10周，对照组、环孢霉素A组、FK506组移植排斥反应指数平均秩分别为13．67、8．07、4．58，对照组排斥反应指数较FK506组（P＝0．02）和环孢霉素A组（P＝0．00）高；环孢霉素A组移植排斥反应指数显著高于FK506组（P＝0．04）。同种异体角膜缘移植术后眼局部应用FK506滴眼液可延迟排斥反应发生，其免疫抑制效果优于环孢霉素A。     

雷公藤多甙防治角膜移植免疫排斥反主尖的实验研究

用兔同种异体角膜移植模型，观察了雷公藤多甙及联合环孢霉素Ａ对植片活时间和移植抗原诱导的迟发型超敏反应的影响。     

角膜移植免疫排斥反应防治研究进展

角膜移植术后发生免疫排斥反应是导致移植手术失败的主要原因。角膜移植与其他器官移植相比，不易发生免疫排斥反应，主要原因：前房的相关免疫偏离状态；血．房水屏障；角膜缺乏血管、淋巴组织；角膜中央区不含成熟抗原提呈细胞；房水中有大量免疫调节分子；眼前节有Fas配基表达等。角膜移植免疫排斥反应是一个复杂的反应过程，一般包括宿主对异体组织抗原的致敏和宿主对异体组织抗原的反应两方面。相应的治疗措施应围绕三方面：（1）阻断宿主对异源组织抗原的敏感性；（2）诱导免疫耐受，使淋巴不激活或活性减低；（3）降低或阻断免疫效应因素对角膜植片的破坏。随着对角膜移植排斥反应机制的深入研究，将有新的治疗措施出现，特别是诱导免疫耐受防治角膜移植排斥反应的研究前景乐观。     

转化生长因子β1在角膜移植术后的免疫抑制作用

对转化生长因子β1的分子结构及生物学功能进行必要介绍,结合角膜移植术后排斥反应的发生特点,以及从T淋巴细胞、树突状细胞、肿瘤坏死因子-α、白细胞介素等多方面对转化生长因子β1在角膜移植术后的免疫抑制作用进行了综述。     

角膜移植术后免疫排斥反应的防治

目的 为控制角膜移植术后发生排斥反应，探讨防治排斥反应的有效途径。方法 根据不同角膜病变排斥反应发生的规律给予不同期的药物联合治疗，降低和控制排斥反应。结果 129眼中47眼(36．43％)发生免疫排斥反应，其中高危角膜病变40眼，非高危角膜病变7眼。有角膜新生血管者占89．36％。排斥反应发生时间为术后3周—3年。经药物联合治疗，角膜排斥反应得到明显的抑制，有效率达63．83％。结论 免疫排斥反应的发生是多因素参与的复杂过程，尤其高危角膜病变，术后出现排斥反应的机率明显增加，发生的时间相对较早，时间跨度较长。因此应根据不同的角膜病变及手术情况，尽早应用免疫抑制剂可明显降低排斥反应的发生率。     

Prevention of experimental corneal allograft rejection in rabbits using cyclosporin-collagen shields

Topical administration of cyclosporin A, a highly hydrophobic cyclic undecapeptide, has been relatively ineffective in preventing corneal allograft rejections due to poor drug penetration. Therefore, we investigated a new continuous-delivery system for cyclosporin A using collagen bandage shields fabricated from porcine scleral tissue. Collagen bandage shields containing 4 mg cyclosporin A were used for the treatment of four corneal allografts embedded in prevascularized rabbit corneas. Four controls were treated with shields containing no cyclosporin A. The shields were changed every 2nd day and signs of rejection were recorded. All controls were rejected by the end of the experiment. Treatment with collagen shields containing cyclosporin A effectively prevented such rejection. The clinical examinations were also confirmed with histopathological analysis. The results indicate that collagen shields can slowly release cyclosporin A and increase the penetration time for the drug. Thus, they are excellent delivery systems for hydrophobic drugs with poor penetration properties.This work was financially supported by the Paulo Foundation, Helsinki, Finland, and by Bausch & Lomb, Inc., Clearwater, Fla, USA     

阻断ICOS抑制兔高危角膜移植排斥反应的实验研究

目的 建立兔角膜移植高危模型,通过阻断ICOS,探讨ICOSmAb对角膜移植排斥反应的影响.方法 将新西兰白兔50只随机分成空白对照组、实验组(植片为浸入含有不同浓度ICOSmAb的中期保存液中)A组(1 mg·L-1 ICOSmAb),B组(10 mg·L-1ICOSmAb),C组(25 mg·L-1 ICOSmAb),D组(250 mg·L-1 ICOSmAb),每组10只兔.观察术后受体植片角膜混浊情况和植片病理改变,应用流式细胞仪检测植片CD4 、CD8 T淋巴细胞表达情况.结果 实验A、B组的植片有较长的生存时间,各实验组及对照组植片平均存活时间(69±34) d、(75±31) d、(45±18) d、(10±3)d、(26±4) d.CD4 、CD8 T淋巴细胞表达明显降低(P＜0.05);A组植片组织病理学检查淋巴细胞浸润较对照组及其他实验组明显减少.结论 应用ICOSmAb阻断ICOS,可以明显抑制高危角膜移植排斥反应.     

Corneal allograft rejection in rabbits

We performed a phase I study to assess the therapeutic efficacy of an anti-T cell monoclonal antibody conjugated with ricin A-chain in a corneal graft rejection model. Corneal allografts were exchanged between Dutch and New Zealand rabbits. Rejections occurred within 16-22 days in untreated animals. Graft rejection was delayed by topical or retrobulbar cyclosporine, but not by subconjunctival injections of a murine anti-rabbit T cell monoclonal antibody, nor by either subconjunctival or intravenous F(ab')2-ricin conjugate.     

Equivalence of topical clobetasone and dexamethasone in experimental corneal allograft rejection.

We produced experimental immune reactions by exchanging peripheral corneal transplants between rabbits. Clobetasone butyrate 0.1% and dexamethasone phosphate 0.1% eye drops were equally effective in delaying corneal allograft rejection.     

角膜移植排斥反应的共焦显微镜研究

目的：探讨角膜移植术后免疫排斥反应的共焦显微镜特征,在细胞水平为该症的基础和临床研究提供活体、三维与实时的科学依据。方法：应用NIDEK公司提供的共焦显微镜,对11例（11眼）发生角膜移植免疫排斥反应的患眼角膜在不同时期行三维实时扫描成像,并用计算机作定性与定量分析。结果：角膜移植免疫排斥反应的共焦显微镜呈现如下特征：①上皮排斥线是由较小的炎症细胞与受损的较大的上皮细胞混合形成的结构;②上皮下浸润表现为体积较小、折射率高的炎症细胞的聚集,上皮下神经纤维水肿呈串珠状改变,浅基层细胞水肿;③基质排斥反应可见角膜基质细胞水肿,胞体变形,数量减少,并见炎症细胞浸润,后者于缝线周围较明显;④内皮排斥线则是由较小的明亮的炎症细胞与核固缩胞体形态异常的内皮细胞混合而成,随着内皮排斥线的发展,内皮 细胞数量减少,体积变大呈伪足状;⑤以上排斥反应均见新生血管长入植片,并与血管壁可见游动的炎症细胞。结论：应用共焦显微镜可在活体上为角膜移植术后免疫排斥反应提供早期诊断与鉴别诊断的科学依据,并在细胞水平对排斥反应的触发与转归进行活体的动态观察。     

Immune mechanisms of corneal allograft rejection

Penetrating keratoplasty has been successfully performed on humans for over 100 years and remains the most common form of solid tissue transplantation. Although corneal allografts enjoy a remarkable degree of immune privilege, immune rejection remains the leading cause of keratoplasty failure. The immunologic basis for corneal allograft rejection was established in animal studies over 50 years ago, yet large gaps remain in our knowledge regarding the cellular and molecular mechanisms of corneal allograft rejection. The enormous redundancy in the mammalian immune system creates a condition that favors the development of multiple independent immune mechanisms that can produce corneal allograft rejection. Although there are few absolute principles, it is certain that the immune rejection of corneal allografts is (1) T cell-dependent, (1) heavily dependent upon CD4(+) T cells, (3) not restricted to either Th1 or Th2 T cell populations, and (4) dependent upon an intact repertoire of resident antigen presenting cells.     

Sustained intraocular rapamycin delivery effectively prevents high-risk corneal allograft rejection and neovascularization in rabbits

PURPOSE: To evaluate the immunosuppressive and antiangiogenic activities of an intraocular rapamycin (RAPA) drug delivery system (DDS) in a rabbit model of high-risk penetrating keratoplasty. METHODS: Forty New Zealand White rabbits with corneal neovascularization underwent allograft cornea transplantation and were randomly divided into four groups: a control group, a glycolide-co-lactide-co-caprolactone copolymer (PGLC)-implanted group, a RAPA eye drop group, and a RAPA-PGLC DDS-implanted group. Graft survival, corneal neovascularization, and RAPA concentration in the aqueous humor were monitored for 90 days. Corneal grafts were also examined by in situ hybridization and immunohistochemistry for proinflammatory gene expression. RESULTS: In the control and PGLC groups, graft rejection occurred within 3 weeks of keratoplasty. In the RAPA eye drop and RAPA-PGLC groups, corneal rejection was significantly delayed, and neovascularization was markedly inhibited. Median graft survival times were 36 and >90 days in the eye drop and RAPA-PGLC groups, respectively. Mean RAPA concentrations in the aqueous humor were 10.7 ng/mL, 12.0 ng/mL, 9.2 ng/mL, and 7.0 ng/mL in the RAPA-PGLC group 2, 4, 8, and 12 weeks after surgery, respectively. By contrast, RAPA was undetectable in the aqueous humor in the eye drop group. High levels of IL-2R, MCP-1, TNF-alpha, and VEGF were detected in the corneal grafts of the control and PGLC groups but not in those of the RAPA-treated groups. CONCLUSIONS: RAPA-PGLC DDS and RAPA eye drops can significantly prolong the survival of allografts at high risk and inhibit corneal neovascularization. However, RAPA-PGLC DDS is far more effective than RAPA eye drops in preventing corneal graft rejection.     

来氟米特活性代谢物A771726对大鼠角膜移植排斥反应的影响

目的探讨来氟米特活性代谢物A771726对大鼠角膜移植排斥反应的抑制作用。方法建立SD-Wistar大鼠同种异体穿透角膜移植模型,随机分组。A组为空白对照组;B、C、D组分别为0．5％、1．0％及2．0％A771726滴眼液组;E组为Wistar大鼠自体移植对照组。术后比较各组角膜植片排斥指数（RI）及植片存活时间,并对植片进行组织学及免疫组织化学染色观察。结果A组角膜植片存活时间为（9．38±2．26）d,B组（10．13±2．41）d,C组（17．57±1．72）d,D组（17．50±2．14）d,E组（〉28．00）d。A组、B组分别与C组、D组植片存活时间差异有统计学意义（P〈0．01）。移植术后10d,A组、B组角膜植片发生排斥反应,植片高表达IFN-γ及ICAM-1;术后20d,C组、D组植片发生排斥反应,植片IFN-γ及ICAM-1表达增高。结论局部应用A771726滴眼液能有效抑制角膜移植排斥反应。     

同种异体角膜移植后角膜内皮细胞的特征表现及生物学意义

同种异体角膜移植目前仍是治疗角膜疾病最为有效的方法,但术后发生的免疫排斥所引起的角膜炎症反应和血管化,最终导致植片水肿,甚至功能丧失仍是造成手术失败的最主要原因.角膜内皮细胞作为免疫赦免及角膜正常生理功能维系的首要屏障,在眼部系统中占据着至关重要的位置.本文就同种异体角膜移植术后免疫的识别,应答和最终反应的各阶段角膜内皮所呈现的特征改变及生物学意义进行阐述.

Abstract：

Allograft corneal transplantation is currently the most effective and optimum method to treat corneal disease, however it is the immune rejection that the main reason for graft edema caused by vascularization and inflammation of the cornea and surgical failure after transplantation. Corneal endothelial cells occupy a crucial position as immune privilege and the primary barriers for maintaining normal physiological function of eye. In this paper, the various stages (recognition, response and reaction of immune system) of corneal endothelial changes in the morphological and biological characteristics had been presented after allograft corneal transplantation.     

Immunology of corneal allograft rejection: HLA-DR antigens on human corneal cells

Human stromal and endothelial cultures were established from corneas obtained from the Maryland Eye Bank. Cultures were incubated in the presence of human gamma interferon for 4 days, trypsinized, washed, and then stained with a monoclonal reagent specific for human Class II (HLA-DR) antigens. Under these conditions, 100% of human corneal endothelial cells and 40 to 70% human corneal stromal cells expressed HLA-DR antigens.