聚乙二醇400对角膜上皮创伤愈合的影响
|
摘要
目的：研究聚乙二醇400对体外培养人角膜上皮细胞生长的影响及其分子机制。
方法：制备含0.1%聚乙二醇400的DMEM/F12培养基培养角膜上皮细胞，无聚乙二醇400的DMEM/F12培养基作为对照组。倒置显微镜观察并照相记录角膜上皮细胞培养24、48、72h时形态；划痕实验检测角膜上皮细胞迁移能力；四甲基偶氮唑蓝法检测角膜上皮细胞生长曲线；流式细胞仪检测角膜上皮细胞细胞周期；RT-PCR检测角膜上皮细胞中bFGF、EGF基因表达水平。
结果：0.1%聚乙二醇400对角膜上皮细胞细胞形态无明显影响，实验组及正常对照组细胞形态均呈典型的多角形。划痕实验中，0.1%聚乙二醇400可以提高角膜上皮细胞迁移能力。MTT提示：0.1%聚乙二醇400对体外培养人CECs的生长有促进作用（P=0.0072）。细胞周期结果显示：0.1%聚乙二醇400体外培养人CECs后细胞增殖指数较对照组明显增高（P=0.0034）。0.1%聚乙二醇400培养人CECs后bFGF和EGF的基因表达水平比对照组高（P<0.05；P<0.01）。
结论：聚乙二醇400可缩短人CECs的细胞周期，上调人CECs bFGF、EGF基因的表达，加速CECs增殖。
目的：研究0.4%聚乙二醇滴眼液对小鼠角膜上皮机械损伤愈合的影响。
方法：选择昆明小鼠30只，实验分为0.4%聚乙二醇滴眼液组、生理盐水组、空白对照组，每组各10只昆明小鼠。用角膜上皮刮匙刮除整个角膜上皮构建角膜上皮机械损伤动物模型，分别于建模后6h、12h、24h、48h及72h裂隙灯下拍照观察角膜上皮愈合情况。
结果：角膜上皮机械损伤6h时，各实验组有效率均为0。12h时，0.4%聚乙二醇滴眼液组有效率为75%，空白对照组和生理盐水组均为0，0.4%聚乙二醇滴眼液组促进上皮愈合有效率明显高于生理盐水组和空白对照组（P=0.001）。24h时，0.4%聚乙二醇滴眼液组有效率为100%，空白对照组和生理盐水组均为16.7%，0.4%聚乙二醇滴眼液组上皮愈合有效率明显高于生理盐水组和空白对照组（P=0.001）。48、72h时，各实验组有效率均为100%。
结论：0.4%聚乙二醇滴眼液能促进角膜上皮机械损伤修复的速度。
目的：研究0.4%聚乙二醇滴眼液对小鼠角膜20%乙醇灼伤愈合的影响。
方法：选择昆明小鼠30只，实验分为0.4%聚乙二醇滴眼液组、生理盐水组、空白对照组，每组各10只昆明小鼠。用沾有20%乙醇的滤片灼伤小鼠角膜构建角膜灼伤动物模型,分别在建模后1d、3d、7d处死各实验组中昆明小鼠3只，摘除眼球，角膜行HE染色以及连接黏附分子、成纤维细胞生长因子、表皮生长因子免疫组织化学研究。
结果：20%乙醇灼伤角膜1d，0.4%聚乙二醇滴眼液组角膜组织中bFGF、EGF的表达较生理盐水组、空白对照组均增高（F=29.853，P=0.001；F=123.965，P=0.000），JAM的表达不增高（F=0.735，P=0.589）；20%乙醇灼伤角膜3d，各实验组角膜组织中bFGF、EGF、JAM的表达无明显差异（F=3.694，P=0.062；F=1.639，P=0.256；F=1.307，P=0.332）；20%乙醇灼伤角膜7d，各实验组角膜组织中bFGF、EGF、JAM的表达无明显差异（F=0.644，P=0.608；F=0.413，P=0.679；F=0.207，P=0.929）。
结论：0.4%聚乙二醇滴眼液在20%乙醇灼伤早期能上调EGF和bFGF的表达，但对JAM的表达无明显影响。
Objective To investigate the effects of polyethylene glycol400on the biologicalcharacteristics of corneal epithelial cells (CECs) and molecular mechanisms thereof.
Methods Polyethylene glycol400was diluted to0.1%with DMEM/F12medium.HCECs were cultured by these medium. DMEM/F12medium without polyethylene glycol400was control group. The effects were tested by four ways. Scarification was used to testthe ability of cell migration; the MTT assay and flow cytometer were respectively used totest the effect on growth curve and cell cycle; RT-PCR was used to measure the expressionof basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in Humancorneal epithelial cells (HCECs).
Result0.1%Polyethylene glycol400has no discernable effects in the morphologyof CECs. Cell migration of CECs was improved by0.1%Polyethylene glycol400. CECscultured in the dilution of polyethylene glycol400solutions and cell cyle measurementsshow that0.1%polyethylene glycol400promotes in vitro HCEC growth(P=0.0072;P=0.0034) and up-regulates the expression of bFGF and EGF in cultured CECs(P<0.05;P<0.01).
Conclusion Polyethylene glycol400does not affect cell morphology and it promotesCEC proliferation via reducing cell cycle and increasing bFGF and EGF expression.
Objective To investigate the effects of0.4%polyethylene glycol eye drop on thehealing of mechanical wound corneal epithelium of mice.
Methods30KM mice were selected for this test. Experiment contained three groupsincluded0.4%polyethylene glycol eye drop group, NS group and control group. And eachgroup had10KM mice.we built the structure of defection of corneal epithelium by curette.We observed corneal healing from shooting under slit lamp after6h,12h,24h,48h and72h.
Result The valid rate of all groups were zero in6h. In12h this rate of0.4%polyethylene glycol eye drop group was75%and the other groups were still zero, the rateof0.4%polyethylene glycol eye drop group became100%and the other groups were both16.7%, both differeces of these times had statistical meaning(P=0.001; P=0.001). And in48and72h all of groups were100%.
Conclusion0.4%polyethylene glycol eye drop could speed repair of cornealepithelium after injury.
Objective To investigate the effects of0.4%polyethylene glycol eye drop on thehealing of burning of corneal epithelium with20%alcohol.
Methods30KM mice were selected for this test. Experiment contained three groupsincluded0.4%polyethylene glycol eye drop group, NS group and control group. And eachgroup had10KM mice.We built the structure of burning of corneal epithelium withfilter-paper contain20%alcohol. We executed three mice in each group after1d,3d and7d.We picked their eyes with HE stain and immunohistochemistry in JAM, bFGF andEGF.
Result The expression of bFGF and EGF in the group of0.4%polyethylene glycoleye drop was more higher than the group of NS and control group after wound in one day.The difference had statistical meaning(F=29.853, P=0.001; F=123.965, P=0.000). Theexpression of JAM had no difference among three groups(F=0.735, P=0.589). After woundin three days the expression of bFGF, EGF and JAM all had no difference among threegroups(F=3.694, P=0.062; F=1.639, P=0.256; F=1.307,P=0.332) as same as in seven days(F=0.644, P=0.608; F=0.413, P=0.679; F=0.207, P=0.929).
Conclusion It could up-regulate the expression of bFGF and EGF after20%alcoholburning. But it had no effects on the expression on JAM.
方法：制备含0.1%聚乙二醇400的DMEM/F12培养基培养角膜上皮细胞，无聚乙二醇400的DMEM/F12培养基作为对照组。倒置显微镜观察并照相记录角膜上皮细胞培养24、48、72h时形态；划痕实验检测角膜上皮细胞迁移能力；四甲基偶氮唑蓝法检测角膜上皮细胞生长曲线；流式细胞仪检测角膜上皮细胞细胞周期；RT-PCR检测角膜上皮细胞中bFGF、EGF基因表达水平。
结果：0.1%聚乙二醇400对角膜上皮细胞细胞形态无明显影响，实验组及正常对照组细胞形态均呈典型的多角形。划痕实验中，0.1%聚乙二醇400可以提高角膜上皮细胞迁移能力。MTT提示：0.1%聚乙二醇400对体外培养人CECs的生长有促进作用（P=0.0072）。细胞周期结果显示：0.1%聚乙二醇400体外培养人CECs后细胞增殖指数较对照组明显增高（P=0.0034）。0.1%聚乙二醇400培养人CECs后bFGF和EGF的基因表达水平比对照组高（P<0.05；P<0.01）。
结论：聚乙二醇400可缩短人CECs的细胞周期，上调人CECs bFGF、EGF基因的表达，加速CECs增殖。
目的：研究0.4%聚乙二醇滴眼液对小鼠角膜上皮机械损伤愈合的影响。
方法：选择昆明小鼠30只，实验分为0.4%聚乙二醇滴眼液组、生理盐水组、空白对照组，每组各10只昆明小鼠。用角膜上皮刮匙刮除整个角膜上皮构建角膜上皮机械损伤动物模型，分别于建模后6h、12h、24h、48h及72h裂隙灯下拍照观察角膜上皮愈合情况。
结果：角膜上皮机械损伤6h时，各实验组有效率均为0。12h时，0.4%聚乙二醇滴眼液组有效率为75%，空白对照组和生理盐水组均为0，0.4%聚乙二醇滴眼液组促进上皮愈合有效率明显高于生理盐水组和空白对照组（P=0.001）。24h时，0.4%聚乙二醇滴眼液组有效率为100%，空白对照组和生理盐水组均为16.7%，0.4%聚乙二醇滴眼液组上皮愈合有效率明显高于生理盐水组和空白对照组（P=0.001）。48、72h时，各实验组有效率均为100%。
结论：0.4%聚乙二醇滴眼液能促进角膜上皮机械损伤修复的速度。
目的：研究0.4%聚乙二醇滴眼液对小鼠角膜20%乙醇灼伤愈合的影响。
方法：选择昆明小鼠30只，实验分为0.4%聚乙二醇滴眼液组、生理盐水组、空白对照组，每组各10只昆明小鼠。用沾有20%乙醇的滤片灼伤小鼠角膜构建角膜灼伤动物模型,分别在建模后1d、3d、7d处死各实验组中昆明小鼠3只，摘除眼球，角膜行HE染色以及连接黏附分子、成纤维细胞生长因子、表皮生长因子免疫组织化学研究。
结果：20%乙醇灼伤角膜1d，0.4%聚乙二醇滴眼液组角膜组织中bFGF、EGF的表达较生理盐水组、空白对照组均增高（F=29.853，P=0.001；F=123.965，P=0.000），JAM的表达不增高（F=0.735，P=0.589）；20%乙醇灼伤角膜3d，各实验组角膜组织中bFGF、EGF、JAM的表达无明显差异（F=3.694，P=0.062；F=1.639，P=0.256；F=1.307，P=0.332）；20%乙醇灼伤角膜7d，各实验组角膜组织中bFGF、EGF、JAM的表达无明显差异（F=0.644，P=0.608；F=0.413，P=0.679；F=0.207，P=0.929）。
结论：0.4%聚乙二醇滴眼液在20%乙醇灼伤早期能上调EGF和bFGF的表达，但对JAM的表达无明显影响。
Objective To investigate the effects of polyethylene glycol400on the biologicalcharacteristics of corneal epithelial cells (CECs) and molecular mechanisms thereof.
Methods Polyethylene glycol400was diluted to0.1%with DMEM/F12medium.HCECs were cultured by these medium. DMEM/F12medium without polyethylene glycol400was control group. The effects were tested by four ways. Scarification was used to testthe ability of cell migration; the MTT assay and flow cytometer were respectively used totest the effect on growth curve and cell cycle; RT-PCR was used to measure the expressionof basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in Humancorneal epithelial cells (HCECs).
Result0.1%Polyethylene glycol400has no discernable effects in the morphologyof CECs. Cell migration of CECs was improved by0.1%Polyethylene glycol400. CECscultured in the dilution of polyethylene glycol400solutions and cell cyle measurementsshow that0.1%polyethylene glycol400promotes in vitro HCEC growth(P=0.0072;P=0.0034) and up-regulates the expression of bFGF and EGF in cultured CECs(P<0.05;P<0.01).
Conclusion Polyethylene glycol400does not affect cell morphology and it promotesCEC proliferation via reducing cell cycle and increasing bFGF and EGF expression.
Objective To investigate the effects of0.4%polyethylene glycol eye drop on thehealing of mechanical wound corneal epithelium of mice.
Methods30KM mice were selected for this test. Experiment contained three groupsincluded0.4%polyethylene glycol eye drop group, NS group and control group. And eachgroup had10KM mice.we built the structure of defection of corneal epithelium by curette.We observed corneal healing from shooting under slit lamp after6h,12h,24h,48h and72h.
Result The valid rate of all groups were zero in6h. In12h this rate of0.4%polyethylene glycol eye drop group was75%and the other groups were still zero, the rateof0.4%polyethylene glycol eye drop group became100%and the other groups were both16.7%, both differeces of these times had statistical meaning(P=0.001; P=0.001). And in48and72h all of groups were100%.
Conclusion0.4%polyethylene glycol eye drop could speed repair of cornealepithelium after injury.
Objective To investigate the effects of0.4%polyethylene glycol eye drop on thehealing of burning of corneal epithelium with20%alcohol.
Methods30KM mice were selected for this test. Experiment contained three groupsincluded0.4%polyethylene glycol eye drop group, NS group and control group. And eachgroup had10KM mice.We built the structure of burning of corneal epithelium withfilter-paper contain20%alcohol. We executed three mice in each group after1d,3d and7d.We picked their eyes with HE stain and immunohistochemistry in JAM, bFGF andEGF.
Result The expression of bFGF and EGF in the group of0.4%polyethylene glycoleye drop was more higher than the group of NS and control group after wound in one day.The difference had statistical meaning(F=29.853, P=0.001; F=123.965, P=0.000). Theexpression of JAM had no difference among three groups(F=0.735, P=0.589). After woundin three days the expression of bFGF, EGF and JAM all had no difference among threegroups(F=3.694, P=0.062; F=1.639, P=0.256; F=1.307,P=0.332) as same as in seven days(F=0.644, P=0.608; F=0.413, P=0.679; F=0.207, P=0.929).
Conclusion It could up-regulate the expression of bFGF and EGF after20%alcoholburning. But it had no effects on the expression on JAM.
引文
[1] McCarty CA，Bansal AK，Livingston PM，et al. The epidemiology of dry eye inMelbourne, Australia[J]. Ophthalmology.1998，105(6):1114-1119.
[2] Shimmura S，Shimazaki J，Tsubota K. Results of a population-based questionnaire onthe symptoms and lifestyles associated with dry eye[J]. Cornea.1999，18(4):408-411.
[3] No authors listed. The definition and classification of dry eye disease: report of thedefinition and classification subcommittee of the International Dry Eye WorkShop.Ocul. Surf.2007，5(2):75-92.
[4] Wilson SE. Inflammation: a unifying theory for the origin of dry eye syndrome[J].Manag. Care.2003,12(12Suppl.):14-19.
[5] Mengher LS，Bron AJ，Tonge SR，et al. A non-invasive instrument for clinicalassessment of the pre-corneal tear film stability[J]. Curr. Eye Res.1985，4(1):1-7.
[6] Nemeth J，Erdelyi B，Csakany B，et al. High-speed videotopographic measurement oftear film build-up time[J]. Invest. Ophthalmol. Vis. Sci.2002，43(6):1783-1790.
[7] Farris RL. Tear osmolarity-a new gold standard?[J]. Adv. Exp. Med. Biol.1994，350:495-503.
[8] Tomlinson A，Khanal S，Ramaesh K，et al. Tear film osmolarity: determination of areferent value for dry eye diagnosis[J]. Invest. Ophthalmol. Vis. Sci.2006，47(10):4309-4315.
[9] Tai MC，Cosar CB，Cohen EJ，et al. The clinical efficacy of silicone punctal plugtherapy[J]. Cornea.2002，21(2):135-139.
[10] Kojima T，Ishida R，Dogru M，et al. The effect of autologous serum eyedrops in thetreatment of severe dry eye disease: a prospective randomized case-control study[J].Am. J. Ophthalmol.2005，139(2):242-246.
[11]唐细兰，叶成添，陈雷宇.玻璃酸钠在眼科的临床研究应用进展[J].中国生化药物杂志.2004，25（2）:123-124.
[12] Shimmura A，Ono M，Shinozaki M，et al. Sodium hyaluronate eyedrops in thetreatment of dry eye[J]. Br J Ophthalmol.1995，79(5):1007-1011.
[13] Christensen MT， Cohen S， Rinehart J， et al. Clinical evaluation of an HP-guar gelable lubricant eye drop for the relief of dryness of the eye[J]. Curr Eye Res.2004，28(1):55–62.
[14] Ousler GW，Michalson C，Christensen MT. An evaluation of tear film breakup timeextension and ocular protection index scores among three marketed lubricant eyedrops[J]. Cornea.2007，26(8):949–952.
[15] Khurana AK，Chaudhary R，Ahluwalia BK，et al. Tear film profile in dry-eye[J]. ActaOphthalmol.1991，69(1):79–86.
[16] Yamada M，Mochizuki H，Kawai M, et al. Fluorophotometric measurement of pH ofhuman tears in vivo[J]. Curr Eye Res.1997，16(5):482–486.
[17] Daush D，Lee S，Dausch S，et al. Comparative Study of Treatment of the Dry EyeSyndrome due to Disturbances of the Tear Film Lipid Layer with Lipid-ContainingTear Substitues[J]. Klin. Mondatsbl. Augenheilke.2006，223(12):974-983.
[1] Calonge M，Amalia E，Diebold Y，et al. Dry Eye Disease as an InflammatoryDisorder[J]. Ocular Immunology&Inflammation.2010，18(4):244–253.
[2]唐细兰，叶成添，黄楚龙.人工泪液的应用[J].食品与药品.2005，7(8A):70-71.
[3]李健和，陈国辉.人工泪制剂的研制开发与临床应用[J].中国医院药学杂志.2003，23(12):756-757.
[4]刘祖国，陈家祺.眼表泪液性疾病的研究[J].中华眼科杂志.2000，36(1):74-76.
[5] Christensen MT， Cohen S， Rinehart J， et al. Clinical evaluation of an HP-guar gelable lubricant eye drop for the relief of dryness of the eye[J]. Curr Eye Res.2004，28(1):55–62.
[6] Ousler GW，Michalson C，Christensen MT. An evaluation of tear film breakup timeextension and ocular protection index scores among three marketed lubricant eyedrops[J]. Cornea.2007，26(8):949–952.
[7] Khurana AK，Chaudhary R，Ahluwalia BK，et al. Tear film profile in dry-eye[J]. ActaOphthalmol.1991，69(1):79–86.
[8] Yamada M，Mochizuki H，Kawai M, et al. Fluorophotometric measurement of pH ofhuman tears in vivo[J]. Curr Eye Res.1997，16(5):482–486.
[9]王铭洁，蔡文杰，曹银祥等.碱性成纤维细胞生长因子促进ECV304细胞迁移的电镜观察[J].复旦学报(医学版).2005，32(6):662-664.
[10] Imanishi J. Expression of cytokines in bacterial and viral infections and theirbiochemical aspects[J]. J Biochem.2000，127(4):525–530.
[11] Hoppenreijs VP，Pels E，Vrensen GF，et a1. Corneal endothelium and growthfactors[J]. Surv Ophthalmol.1996，41(2):151-164.
[12] Heather CB，John M. Growth factors in corneal wound healing following refractivesurgery: A review[J]. Acta Ophthalmol Scand.2002，80(3):238-247.
[13] Rose K，Pallast S，Klumpp S, et al. ATP-binding on Fibroblast Growth Factor2Partially Overlaps with the Heparin-binding Domain[J]. J Biochem.2008，144(3):343–347.
[14]刘扬，刘祖国.表皮生长因子及其受体在眼表创伤愈合中的作用[J].中华眼科杂志.2007，43(10):953-956.
[15] Katherine JB，Kiang A，Rodriguez JW，et al. EGF and bFGF Promote Invasion ThatIs Modulated by PI3/Akt Kinase and Erk in Vestibular Schwannoma[J]. Otology&Neurotology,2011,32(2):308-314.
[16] Chandrasekher G， Bazan HE. Corneal epithelial wound healing increases theexpression but not long lasting activation of the p85alpha subunit ofphosphatidylinositol-3kinase[J]. Curt Eye Res.1999，18(3):168-176.
[17] Imanishi J，Kamiyama K，Ignchi I，et a1.Growth factors：importance in wound healingand maintenance of transparency of the cornea[J]. Prog Retin Eye Res.2000，19(1):113-129.
[18] Yo N，Chic S，Shigeru K. The epidermal growth factor receptor(EGFR)：Role incorneal wound healing and homeostasis[J]. Exp Eye Res.2001，72(5):511-517.
[19] Wilson SE，Chen L，Mohan RR，et a1. Expression of HGF, KGF, EGF and receptormessenger RNAs following corneal epithelial wounding[J]. Exp Eye Res.1999，68(4):377-397.
[20] Lee JS，Uu JJ，Hong JW，et a1. Diferential expression analysis by gene array of cellcycle modulators in human corneal epithelial cells stimulated with epidermal growthfactor(EGF), hepatocyte growth factor(HGF), or keratinocyte growth factor(KGF)[J].Curt Eye Res.2001，23(1):69-76.
[1] Robert C，Scaffidi BS，Donald R，et al. Comparison of the Efficacy of Two LipidEmulsion Eyedrops in Increasing Tear Film Lipid Layer Thickness[J]. Eye&ContactLens2007，33(1):38-44.
[2] Heather CB, John M. Growth factors in corneal wound healing following refractivesurgery: A review[J].Acta Ophthalmol Scand.2002，80(3):238-247.
[3]颞庆珠，尹树国.碱性成纤维细胞生长因子治疗兔角膜上皮及基质损伤的实验研究[J].中国实用眼科杂志.2000，18(6):340–343.
[4] Imanishi J，Kamiyama K，Ignchi I，et a1. Growth factors：importance in wound healingand maintenance of transparency of the cornea[J]. Prog Retin Eye Res.2000，19(1):113-129.
[5]郑荣领，金秀英，杨宝玲，等.基因重组人表皮生皮因子治疗兔角膜损伤的研究[J].中华眼科杂志.1998，34(3):215–217.
[6]Chung JH，Fagerholm P. Treatment of rabbit corneal alkali wounds with humanepidermal growth factor[J]. Cornea.1989，8(2):l22-128.
[7]李华，宋徽.小牛血去蛋白提取物凝胶与透明质酸钠治疗角膜上皮损伤疗效分析[J].武警医学院学报.2010，19(3):203–204.
[8] Martin P. Wound healing-aiming for perfect skin regeneration[J]. Science.1997，276(5309):75-81.
[9] Zieske J D. Extracellular matrix and wound healing[J]. Curt Opin Ophthalmol.2001，12(4):237-241.
[10] Christensen MT， Cohen S， Rinehart J， et al. Clinical evaluation of an HP-guar gelable lubricant eye drop for the relief of dryness of the eye[J]. Curr Eye Res.2004，28(1):55–62.
[11] Khurana AK，Chaudhary R，Ahluwalia BK，et al. Tear film profile in dry-eye[J]. ActaOphthalmol.1991，69(1):79–86.
[12] Yamada M，Mochizuki H，Kawai M, et al. Fluorophotometric measurement of pH ofhuman tears in vivo[J]. Curr Eye Res.1997，16(5):482–486.
[1] Wilson SE, Liu JJ, Mohan RR. Stromal-epithelial interactions in the cornea[J]. ProgRetin Eye Res.1999，18(3):293-309.
[2] Imanishi J. Expression of cytokines in bacterial and viral infections and theirbiochemical aspects[J]. J Biochem.2000，127(4):525-530.
[3]Folkman, J. The role of angiogenesis in tumor growth and metastasis[J]. Semin Oncol.2002，29(6Suppl16):3-9.
[4] Imanishi J，Kamiyama K，Ignchi I，et a1. Growth factors：importance in wound healingand maintenance of transparency of the cornea[J]. Prog Retin Eye Res.2000，19(1):113-129.
[5]陈立忠，洪晶，海老原，等.连接黏附分子-1和咬合蛋白在人角膜上皮中的表达眼科新进展[J].2007，27(9)：666-669.
[6] Bazzoni G，Dejana E. Endothelial cell-to-cell junctions: molecular organization androle in vascular homeostasis[J]. Physiological Reviews.2004，84(3):869–901.
[7] Bradfield PF，Nourshargh S，Aurrand-Lions M，et al. JAM family and related proteinsin leukocyte migration (Vestweber series)[J]. Arteriosclerosis Thrombosis andVascular Biology.2007，27(10):2104–2112.
[8] Vestweber D. Adhesion and signaling molecules controlling the transmigration ofleukocytes through endothelium[J]. Immunological Reviews.2007，218:178–196.
[9] Mandell KJ，Berglin L，Severson EA，et al. Expression of JAM-A in the HumanCorneal Endothelium and Retinal Pigment Epithelium: Localization and Evidence forRole in Barrier Function[J]. Investigative Ophthalmology&Visual Science.2007，48(9):3928-3936.
[10] Heather CB, John M. Growth factors in corneal wound healing following refractivesurgery: A review[J].Acta Ophthalmol Scand.2002，80(3):238-247.
[11] Wilson SE，Mohan RR，Hong JW，et a1. The wound healing response after laser insitu keratomileusis and photorefractive keratectomy：elusive control of biologicalvariability and effect on custom laser vision correction[J]. Arch Ophthalmol.2001，l19(6):889-896.
[12]颞庆珠，尹树国.碱性成纤维细胞生长因子治疗兔角膜上皮及基质损伤的实验研究[J].中国实用眼科杂志.2000，18(6):340–343.
[13]郑荣领，金秀英，杨宝玲，等.基因重组人表皮生皮因子治疗兔角膜损伤的研究[J].中华眼科杂志.1998，34(3):215–217.
[14] Weber C，Fraemohs L，Dejana E. The role of junctional adhesion molecules invascular inflammation[J]. Nature Reviews Immunology.2007，7(6):467-477.
[15] Vesselina GC，Meghna UN，Naik UP. Fibroblast Growth Factor-2Failed to InduceAngiogenesisin Junctional Adhesion Molecule-A–Deficient Mice[J]. ArteriosclerThromb Vasc Biol.2006，26(9):2005-2011.
[16] Naik MU， Naik UP. Junctional adhesion molecule-A-induced endothelial cellmigration on vitronectin is integrin alpha v beta3specific[J]. J Cell Sci.2006，119(Pt3):490–499.
[1] McCarty CA，Bansal AK，Livingston PM，et al. The epidemiology of dry eye inMelbourne, Australia[J]. Ophthalmology.1998，105(6):1114-1119.
[2] Shimmura S，Shimazaki J，Tsubota K. Results of a population-based questionnaire onthe symptoms and lifestyles associated with dry eye[J]. Cornea.1999，18(4):408-411.
[3] No authors listed. The definition and classification of dry eye disease: report of thedefinition and classification subcommittee of the International Dry Eye WorkShop.Ocul. Surf.2007，5(2):75-92.
[4] Management and therapy of dry eye disease: report of the Management andTherapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf2007;5:163–178.
[5] Lemp MA. Management of dry eye disease[J]. Am J Manag Care.2008，14(3suppl):S88–101.
[6] Wilson SE, Stulting RD. Agreement of physician treatment practices with theinternational task force guidelines for diagnosis and treatment of dry eye disease[J].Cornea.2007，26(3):284-289.
[7] McCann LC，Tomlinson A，Pearce EI，et al. Effectiveness of Artificial Tears in theManagement of Evaporative Dry Eye[J]. Cornea.2012，31(1):1-5.
[8] Luchs J. Efficacy of topical azithromycin ophthalmic solution1%in the treatment ofposterior blepharitis[J]. Adv Ther.2008，25(9):858-870.
[9] Alkhamesi NA，Martin J，Schlachta CM. Cost-efficiency of laparoscopic versus opencolon surgery in a tertiary care center[J]. Surg Endosc.2011，25(11):3597-3604.
[10] Balkhy HH，El Beltagy KE，El-Saed A，et al. Benchmarking of percutaneous injuriesat a teaching tertiary care center in Saudi Arabia relative to United States hospitalsparticipating in the Exposure Prevention Information Network[J]. Am J Infect Control.2011，39(7):560-565.
[11] Matsuda S， Koyasu S. Mechanisms of action of cyclosporine[J].Immunopharmacology.2000，47(2-3):119-125.
[12] Strong B，Farley W，Stern ME，et al. Topical cyclosporine inhibits conjunctivalepithelial apoptosis in experimental murine keratoconjunctivitis sicca[J]. Cornea.2005，24(1):80-85.
[13] Kunert KS，Tisdale AS，Stern ME，et al. Analysis of topical cyclosporine treatmentof patients with dry eye syndrome[J]. Arch Ophthalmol.2000，118(11):1489-1496.
[14] Moon JW，Lee HJ，Shin KC，et al. Short term effects of topical cyclosporine andviscoelastic on the ocular surface in patients with dry eye[J]. Korean J Ophthalmol.2007，21(4):189-194.
[15] Pflugfelder SC，De Paiva CS，Villarreal AL，et al. Effects of sequential artificial tearand cyclosporine emulsion therapy on conjunctival goblet cell density andtransforming growth factor-beta2production[J]. Cornea.2008，27(1):64-69.
[16] Kim EC，Choi JS，Joo CK. A comparison of vitamin a and cyclosporine a0.05%eyedrops for treatment of dry eye syndrome[J]. Am J Ophthalmol.2009，147(2):206-213.
[17] Demiryay E，Yaylal V，Cetin EN，et al. Effects of Topical Cyclosporine A PlusArtificial Tears Versus Artificial Tears Treatment on Conjunctival Goblet CellDensity in Dysfunctional Tear Syndrome[J]. Eye&Contact Lens.2011，37(5):312-315.
[18] Prabhasawat P，Tesavibul N，Mahawong W, et al. A Randomized Double-MaskedStudy of0.05%Cyclosporine Ophthalmic Emulsion in the Treatment of MeibomianGland Dysfunction[J]. Cornea.2012，Jan.
[19] Su YM，Perry HD，Barsam A，et al. The Effect of Decreasing the Dosage ofCyclosporine A0.05%on Dry Eye Disease After1Year of Twice-Daily Therapy[J].Cornea.2011，30(10):1098-1104.
[20] Avunduk AM, Avunduk MC, Varnell ED, et al. The comparison of efficacies oftopical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: aclinical and immunocytochemical study[J]. Am. J. Opthalmol.2003，136(4):593-602.
[21] Pflugfelder SC，Maskin Sl，Anderson B，et al. A randomized, double-masked,placebo-controlled, multicenter comparsion of loteprednol etabonate ophthalmicsuspension,0.5%, and placebo for treatment of keratoconjunctivitis sicca in patientswith delayed tear clearance[J]. Am. J. Opthalmol.2004，138(8):444-457.
[22]Avunduk AM，Avunduk MC，Varnell ED，et al. The comparison of efficacies oftopical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: aclinical and immunocytochemical study[J]. Am J Ophthalmol.2003，136(4):593-602.
[23] Lee HK，Ryu IH，Seo KY，et al. Topical0.1%Prednisolone Lowers Nerve GrowthFactor Expression in Keratoconjunctivitis Sicca Patients[J]. Opthalmology.2006，113(2):198-205.
[24] Fox RI，Chan R，Michelson JB，et al. Beneficial effect of artificial tears made withautologous serum in patients with keratoconjunctivitis sicca[J]. Arthritis Rheu.1984，27(4):459-461.
[25] Kojima T，Ishida R，Dogru M，et al. The effect of autologous serum eye drops in thetreatment of severe dry eye disease: a prospective randomized case-control study[J].Am J Ophthalmol.2005，139(3):242-246.
[26] Lo′pez-Plandolit S，Morales MC，Freire V，et al. Efficacy of Plasma Rich in GrowthFactors for the Treatment of Dry Eye[J]. Cornea.2011，30(12):1312-1317.
[27] Rocha G，Acera A，Dura′n JA. Laser in situ keratomileusis flap necrosis aftertrigeminal nerve palsy[J]. Arch Ophthalmol.2007，125(10):1423-1425.
[28] Lo′pez-Plandolit S, Morales MC, Freire V, et al. Plasma rich in growth factors (PRGF)as a therapeutic agent for severe persistent corneal epithelial defects[J]. Cornea.2010，29(8):843-848.
[29] Matta JA， Miyares RL， Ahern GA. TRPV1is a novel target for omega-3polyunsaturated fatty acids[J]. J Physiology.2007，578(pt2):397-411.
[30] Xu ZZ，Zhang L，Liu T，et al. Resolvins RvE1and RvD1attenuate inflammatorypain via central and peripheral actions[J]. Nature Med.2010，16(5):592-597.
[31] Serhan CN. Systems approach with inflammatory exudates uncovers novelanti-inflammatory and pro-resolving mediators[J]. Prostaglandins Leukot Essent FattyAcids.2008，79(3-5):157-163.
[32] Aragona P，Bucolo C，Spinella R，et al. Systemic omega-6essential fatty acidtreatment and pge1tear content in Sjogren’s syndrome patients[J]. Invest OphthalmolVis Sci.2005，46(12):4474-4479.
[33] Kokke KH，Morris JA，Lawrenson JG. Oral omega-6essential fatty acid treatment incontact lens associated dry eye[J]. Cont Lens Anterior Eye.2008，31(3):141-146.
[34] Creuzot C，Passemard M，Viau S，et al. Improvement of dry eye symptoms withpolyunsaturated fatty acids[J]. J Fr Ophtalmol.2006，29(8):868-873.
[35] de Paiva CS， Schwartz CZ，Gj rstrup P，et al. Resolvin E1(RX-10001) ReducesCorneal Epithelial Barrier Disruption and Protects Against Goblet Cell Loss in aMurine Model of Dry Eye[J]. Cornea.2012，Jan17.
[36] Ja¨rvinen RL，Larmo PS，Seta¨la¨ NL，et al. Effects of Oral Sea Buckthorn Oil on TearFilm Fatty Acids in Individuals With Dry Eye[J]. Cornea.2011，30(9):1013-1019.
[37] Kokke KH，Morris JA，Lawrenson JG. Oral omega-6essential fatty acid treatment incontact lens associated dry eye[J]. Cont Lens Anterior Eye.2008，31(3):141-146.
[38] Ono M，Rocha FJ，Sullivan DA，et al. Immunocytochemical location and hormonalcontrol of androgen receptors in lacrimal tissues of the female MRL/Mp-lpr/lpr mousemodel of sjogren’s syndrome[J]. Exp Eye Res.1995，61(6):659-666.
[39] Sullivan DA，Jensen RV，Suzuki T，et al. Do sex steroids exert sex-specific and/oropposite effects on gene expression in lacrimal and meibomian glands?[J]. Mol vis.2009，15(10):1553-1572.
[40]赫凤芹，张明昌，姜发纲.性激素受体在人眼角膜组织中的表达[J].临床眼科杂志.2005，13(3):274-276.
[41] Krenzer KL，Dana MR，Ullman MD，et al. Effects of androgen deficiency on thehuman meibomian gland and ocular surface[J]. J clin Endocrinol Metab.2000，85(12):4874-4882.
[42] Sullivan DA，Krenzer KL，Sullivan BD，et al. Does androgen insufficiency causelacrimal gland inflammation and aqueous tear deficiency?[J]. Invest. Ophthalmol.Vis. Sci.1999，40(6):1261-1265.
[43] Worda C，Nepp J，Huber JC，et al. Treatment of keratoconjunctivitis sicca with topicalandrogen[J]. Maturitas.2001，37(3):209-212.
[44] Deshande A，Heller J，Gurny R. Bioerodible polymers for ocular delivery[J]. Crit. Rev.Ther. Drug Carrier Syst.1998，15(4):381-420.
[45] Calvo P，Sanchez A，Marta-nez J，et al. Polyester nanocapsules as new topical oculardelivery systems for cyclosporin A[J]. Pharmaceutical Research.1996，13(2):311-315.
[46] De Campos AM，Sanchez A，Alonso MJ. Chitosan nanparticles: a new vehicle for theimprovement of the delivery of drugs to the ocular surface. Application to cyclosporinA[J]. Int. J. Pharm.2001，224(1-2):159-168.
[47] Goto E，Yagi Y，Kaido M，et al. Improved functional visual acuity after punctalocclusion in dry eye patients[J]. Am J Ophthalmol.2003，135(5):704-705.
[48] Benson DR，Hemmady PB，Snyder RW，et al. Efficacy of laser punctal occlusion[J].Ophthalmology.1992，99(4):618-621.
[49] McDonald M，D'Aversa G，Perry HD，et al. Hydroxypropyl cellulose ophthalmicinserts (lacrisert) reduce the signs and symptoms of dry eye syndrome and improvepatient quality of life[J]. Trans. Am. Ophthalmol. Soc.2009，107:214-221.
[50] Geerling G，Sieg P. Transplantation of the major salivary glands[J]. Dev. Ophthalmol.2008，41:255-268.
[51] Lane SS，DuBiner HB，Epstein RJ，et al. A New System, the LipiFlow, for theTreatment of Meibomian Gland Dysfunction (MGD)[J]. Cornea.2012，Jan4.
[52] Blom M，Kopp S，Lundeberg T. Prognostic value of the pilocarpine test to identifypatients who may obtain long-term relief from xerostomia by acupuncturetreatment[J]. Arch. Otolaryngol. Head Neck Surg.1999，125(5):561-566.
[53] Nepp J，Derbolav A，Haslinger-Akramian J，et al. Effects of acupuncture inkeratoconjunctivitis sicca[J]. Klin. Monatsbl. Augenheilked.1999，215(4):228-232.
[2] Shimmura S，Shimazaki J，Tsubota K. Results of a population-based questionnaire onthe symptoms and lifestyles associated with dry eye[J]. Cornea.1999，18(4):408-411.
[3] No authors listed. The definition and classification of dry eye disease: report of thedefinition and classification subcommittee of the International Dry Eye WorkShop.Ocul. Surf.2007，5(2):75-92.
[4] Wilson SE. Inflammation: a unifying theory for the origin of dry eye syndrome[J].Manag. Care.2003,12(12Suppl.):14-19.
[5] Mengher LS，Bron AJ，Tonge SR，et al. A non-invasive instrument for clinicalassessment of the pre-corneal tear film stability[J]. Curr. Eye Res.1985，4(1):1-7.
[6] Nemeth J，Erdelyi B，Csakany B，et al. High-speed videotopographic measurement oftear film build-up time[J]. Invest. Ophthalmol. Vis. Sci.2002，43(6):1783-1790.
[7] Farris RL. Tear osmolarity-a new gold standard?[J]. Adv. Exp. Med. Biol.1994，350:495-503.
[8] Tomlinson A，Khanal S，Ramaesh K，et al. Tear film osmolarity: determination of areferent value for dry eye diagnosis[J]. Invest. Ophthalmol. Vis. Sci.2006，47(10):4309-4315.
[9] Tai MC，Cosar CB，Cohen EJ，et al. The clinical efficacy of silicone punctal plugtherapy[J]. Cornea.2002，21(2):135-139.
[10] Kojima T，Ishida R，Dogru M，et al. The effect of autologous serum eyedrops in thetreatment of severe dry eye disease: a prospective randomized case-control study[J].Am. J. Ophthalmol.2005，139(2):242-246.
[11]唐细兰，叶成添，陈雷宇.玻璃酸钠在眼科的临床研究应用进展[J].中国生化药物杂志.2004，25（2）:123-124.
[12] Shimmura A，Ono M，Shinozaki M，et al. Sodium hyaluronate eyedrops in thetreatment of dry eye[J]. Br J Ophthalmol.1995，79(5):1007-1011.
[13] Christensen MT， Cohen S， Rinehart J， et al. Clinical evaluation of an HP-guar gelable lubricant eye drop for the relief of dryness of the eye[J]. Curr Eye Res.2004，28(1):55–62.
[14] Ousler GW，Michalson C，Christensen MT. An evaluation of tear film breakup timeextension and ocular protection index scores among three marketed lubricant eyedrops[J]. Cornea.2007，26(8):949–952.
[15] Khurana AK，Chaudhary R，Ahluwalia BK，et al. Tear film profile in dry-eye[J]. ActaOphthalmol.1991，69(1):79–86.
[16] Yamada M，Mochizuki H，Kawai M, et al. Fluorophotometric measurement of pH ofhuman tears in vivo[J]. Curr Eye Res.1997，16(5):482–486.
[17] Daush D，Lee S，Dausch S，et al. Comparative Study of Treatment of the Dry EyeSyndrome due to Disturbances of the Tear Film Lipid Layer with Lipid-ContainingTear Substitues[J]. Klin. Mondatsbl. Augenheilke.2006，223(12):974-983.
[1] Calonge M，Amalia E，Diebold Y，et al. Dry Eye Disease as an InflammatoryDisorder[J]. Ocular Immunology&Inflammation.2010，18(4):244–253.
[2]唐细兰，叶成添，黄楚龙.人工泪液的应用[J].食品与药品.2005，7(8A):70-71.
[3]李健和，陈国辉.人工泪制剂的研制开发与临床应用[J].中国医院药学杂志.2003，23(12):756-757.
[4]刘祖国，陈家祺.眼表泪液性疾病的研究[J].中华眼科杂志.2000，36(1):74-76.
[5] Christensen MT， Cohen S， Rinehart J， et al. Clinical evaluation of an HP-guar gelable lubricant eye drop for the relief of dryness of the eye[J]. Curr Eye Res.2004，28(1):55–62.
[6] Ousler GW，Michalson C，Christensen MT. An evaluation of tear film breakup timeextension and ocular protection index scores among three marketed lubricant eyedrops[J]. Cornea.2007，26(8):949–952.
[7] Khurana AK，Chaudhary R，Ahluwalia BK，et al. Tear film profile in dry-eye[J]. ActaOphthalmol.1991，69(1):79–86.
[8] Yamada M，Mochizuki H，Kawai M, et al. Fluorophotometric measurement of pH ofhuman tears in vivo[J]. Curr Eye Res.1997，16(5):482–486.
[9]王铭洁，蔡文杰，曹银祥等.碱性成纤维细胞生长因子促进ECV304细胞迁移的电镜观察[J].复旦学报(医学版).2005，32(6):662-664.
[10] Imanishi J. Expression of cytokines in bacterial and viral infections and theirbiochemical aspects[J]. J Biochem.2000，127(4):525–530.
[11] Hoppenreijs VP，Pels E，Vrensen GF，et a1. Corneal endothelium and growthfactors[J]. Surv Ophthalmol.1996，41(2):151-164.
[12] Heather CB，John M. Growth factors in corneal wound healing following refractivesurgery: A review[J]. Acta Ophthalmol Scand.2002，80(3):238-247.
[13] Rose K，Pallast S，Klumpp S, et al. ATP-binding on Fibroblast Growth Factor2Partially Overlaps with the Heparin-binding Domain[J]. J Biochem.2008，144(3):343–347.
[14]刘扬，刘祖国.表皮生长因子及其受体在眼表创伤愈合中的作用[J].中华眼科杂志.2007，43(10):953-956.
[15] Katherine JB，Kiang A，Rodriguez JW，et al. EGF and bFGF Promote Invasion ThatIs Modulated by PI3/Akt Kinase and Erk in Vestibular Schwannoma[J]. Otology&Neurotology,2011,32(2):308-314.
[16] Chandrasekher G， Bazan HE. Corneal epithelial wound healing increases theexpression but not long lasting activation of the p85alpha subunit ofphosphatidylinositol-3kinase[J]. Curt Eye Res.1999，18(3):168-176.
[17] Imanishi J，Kamiyama K，Ignchi I，et a1.Growth factors：importance in wound healingand maintenance of transparency of the cornea[J]. Prog Retin Eye Res.2000，19(1):113-129.
[18] Yo N，Chic S，Shigeru K. The epidermal growth factor receptor(EGFR)：Role incorneal wound healing and homeostasis[J]. Exp Eye Res.2001，72(5):511-517.
[19] Wilson SE，Chen L，Mohan RR，et a1. Expression of HGF, KGF, EGF and receptormessenger RNAs following corneal epithelial wounding[J]. Exp Eye Res.1999，68(4):377-397.
[20] Lee JS，Uu JJ，Hong JW，et a1. Diferential expression analysis by gene array of cellcycle modulators in human corneal epithelial cells stimulated with epidermal growthfactor(EGF), hepatocyte growth factor(HGF), or keratinocyte growth factor(KGF)[J].Curt Eye Res.2001，23(1):69-76.
[1] Robert C，Scaffidi BS，Donald R，et al. Comparison of the Efficacy of Two LipidEmulsion Eyedrops in Increasing Tear Film Lipid Layer Thickness[J]. Eye&ContactLens2007，33(1):38-44.
[2] Heather CB, John M. Growth factors in corneal wound healing following refractivesurgery: A review[J].Acta Ophthalmol Scand.2002，80(3):238-247.
[3]颞庆珠，尹树国.碱性成纤维细胞生长因子治疗兔角膜上皮及基质损伤的实验研究[J].中国实用眼科杂志.2000，18(6):340–343.
[4] Imanishi J，Kamiyama K，Ignchi I，et a1. Growth factors：importance in wound healingand maintenance of transparency of the cornea[J]. Prog Retin Eye Res.2000，19(1):113-129.
[5]郑荣领，金秀英，杨宝玲，等.基因重组人表皮生皮因子治疗兔角膜损伤的研究[J].中华眼科杂志.1998，34(3):215–217.
[6]Chung JH，Fagerholm P. Treatment of rabbit corneal alkali wounds with humanepidermal growth factor[J]. Cornea.1989，8(2):l22-128.
[7]李华，宋徽.小牛血去蛋白提取物凝胶与透明质酸钠治疗角膜上皮损伤疗效分析[J].武警医学院学报.2010，19(3):203–204.
[8] Martin P. Wound healing-aiming for perfect skin regeneration[J]. Science.1997，276(5309):75-81.
[9] Zieske J D. Extracellular matrix and wound healing[J]. Curt Opin Ophthalmol.2001，12(4):237-241.
[10] Christensen MT， Cohen S， Rinehart J， et al. Clinical evaluation of an HP-guar gelable lubricant eye drop for the relief of dryness of the eye[J]. Curr Eye Res.2004，28(1):55–62.
[11] Khurana AK，Chaudhary R，Ahluwalia BK，et al. Tear film profile in dry-eye[J]. ActaOphthalmol.1991，69(1):79–86.
[12] Yamada M，Mochizuki H，Kawai M, et al. Fluorophotometric measurement of pH ofhuman tears in vivo[J]. Curr Eye Res.1997，16(5):482–486.
[1] Wilson SE, Liu JJ, Mohan RR. Stromal-epithelial interactions in the cornea[J]. ProgRetin Eye Res.1999，18(3):293-309.
[2] Imanishi J. Expression of cytokines in bacterial and viral infections and theirbiochemical aspects[J]. J Biochem.2000，127(4):525-530.
[3]Folkman, J. The role of angiogenesis in tumor growth and metastasis[J]. Semin Oncol.2002，29(6Suppl16):3-9.
[4] Imanishi J，Kamiyama K，Ignchi I，et a1. Growth factors：importance in wound healingand maintenance of transparency of the cornea[J]. Prog Retin Eye Res.2000，19(1):113-129.
[5]陈立忠，洪晶，海老原，等.连接黏附分子-1和咬合蛋白在人角膜上皮中的表达眼科新进展[J].2007，27(9)：666-669.
[6] Bazzoni G，Dejana E. Endothelial cell-to-cell junctions: molecular organization androle in vascular homeostasis[J]. Physiological Reviews.2004，84(3):869–901.
[7] Bradfield PF，Nourshargh S，Aurrand-Lions M，et al. JAM family and related proteinsin leukocyte migration (Vestweber series)[J]. Arteriosclerosis Thrombosis andVascular Biology.2007，27(10):2104–2112.
[8] Vestweber D. Adhesion and signaling molecules controlling the transmigration ofleukocytes through endothelium[J]. Immunological Reviews.2007，218:178–196.
[9] Mandell KJ，Berglin L，Severson EA，et al. Expression of JAM-A in the HumanCorneal Endothelium and Retinal Pigment Epithelium: Localization and Evidence forRole in Barrier Function[J]. Investigative Ophthalmology&Visual Science.2007，48(9):3928-3936.
[10] Heather CB, John M. Growth factors in corneal wound healing following refractivesurgery: A review[J].Acta Ophthalmol Scand.2002，80(3):238-247.
[11] Wilson SE，Mohan RR，Hong JW，et a1. The wound healing response after laser insitu keratomileusis and photorefractive keratectomy：elusive control of biologicalvariability and effect on custom laser vision correction[J]. Arch Ophthalmol.2001，l19(6):889-896.
[12]颞庆珠，尹树国.碱性成纤维细胞生长因子治疗兔角膜上皮及基质损伤的实验研究[J].中国实用眼科杂志.2000，18(6):340–343.
[13]郑荣领，金秀英，杨宝玲，等.基因重组人表皮生皮因子治疗兔角膜损伤的研究[J].中华眼科杂志.1998，34(3):215–217.
[14] Weber C，Fraemohs L，Dejana E. The role of junctional adhesion molecules invascular inflammation[J]. Nature Reviews Immunology.2007，7(6):467-477.
[15] Vesselina GC，Meghna UN，Naik UP. Fibroblast Growth Factor-2Failed to InduceAngiogenesisin Junctional Adhesion Molecule-A–Deficient Mice[J]. ArteriosclerThromb Vasc Biol.2006，26(9):2005-2011.
[16] Naik MU， Naik UP. Junctional adhesion molecule-A-induced endothelial cellmigration on vitronectin is integrin alpha v beta3specific[J]. J Cell Sci.2006，119(Pt3):490–499.
[1] McCarty CA，Bansal AK，Livingston PM，et al. The epidemiology of dry eye inMelbourne, Australia[J]. Ophthalmology.1998，105(6):1114-1119.
[2] Shimmura S，Shimazaki J，Tsubota K. Results of a population-based questionnaire onthe symptoms and lifestyles associated with dry eye[J]. Cornea.1999，18(4):408-411.
[3] No authors listed. The definition and classification of dry eye disease: report of thedefinition and classification subcommittee of the International Dry Eye WorkShop.Ocul. Surf.2007，5(2):75-92.
[4] Management and therapy of dry eye disease: report of the Management andTherapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf2007;5:163–178.
[5] Lemp MA. Management of dry eye disease[J]. Am J Manag Care.2008，14(3suppl):S88–101.
[6] Wilson SE, Stulting RD. Agreement of physician treatment practices with theinternational task force guidelines for diagnosis and treatment of dry eye disease[J].Cornea.2007，26(3):284-289.
[7] McCann LC，Tomlinson A，Pearce EI，et al. Effectiveness of Artificial Tears in theManagement of Evaporative Dry Eye[J]. Cornea.2012，31(1):1-5.
[8] Luchs J. Efficacy of topical azithromycin ophthalmic solution1%in the treatment ofposterior blepharitis[J]. Adv Ther.2008，25(9):858-870.
[9] Alkhamesi NA，Martin J，Schlachta CM. Cost-efficiency of laparoscopic versus opencolon surgery in a tertiary care center[J]. Surg Endosc.2011，25(11):3597-3604.
[10] Balkhy HH，El Beltagy KE，El-Saed A，et al. Benchmarking of percutaneous injuriesat a teaching tertiary care center in Saudi Arabia relative to United States hospitalsparticipating in the Exposure Prevention Information Network[J]. Am J Infect Control.2011，39(7):560-565.
[11] Matsuda S， Koyasu S. Mechanisms of action of cyclosporine[J].Immunopharmacology.2000，47(2-3):119-125.
[12] Strong B，Farley W，Stern ME，et al. Topical cyclosporine inhibits conjunctivalepithelial apoptosis in experimental murine keratoconjunctivitis sicca[J]. Cornea.2005，24(1):80-85.
[13] Kunert KS，Tisdale AS，Stern ME，et al. Analysis of topical cyclosporine treatmentof patients with dry eye syndrome[J]. Arch Ophthalmol.2000，118(11):1489-1496.
[14] Moon JW，Lee HJ，Shin KC，et al. Short term effects of topical cyclosporine andviscoelastic on the ocular surface in patients with dry eye[J]. Korean J Ophthalmol.2007，21(4):189-194.
[15] Pflugfelder SC，De Paiva CS，Villarreal AL，et al. Effects of sequential artificial tearand cyclosporine emulsion therapy on conjunctival goblet cell density andtransforming growth factor-beta2production[J]. Cornea.2008，27(1):64-69.
[16] Kim EC，Choi JS，Joo CK. A comparison of vitamin a and cyclosporine a0.05%eyedrops for treatment of dry eye syndrome[J]. Am J Ophthalmol.2009，147(2):206-213.
[17] Demiryay E，Yaylal V，Cetin EN，et al. Effects of Topical Cyclosporine A PlusArtificial Tears Versus Artificial Tears Treatment on Conjunctival Goblet CellDensity in Dysfunctional Tear Syndrome[J]. Eye&Contact Lens.2011，37(5):312-315.
[18] Prabhasawat P，Tesavibul N，Mahawong W, et al. A Randomized Double-MaskedStudy of0.05%Cyclosporine Ophthalmic Emulsion in the Treatment of MeibomianGland Dysfunction[J]. Cornea.2012，Jan.
[19] Su YM，Perry HD，Barsam A，et al. The Effect of Decreasing the Dosage ofCyclosporine A0.05%on Dry Eye Disease After1Year of Twice-Daily Therapy[J].Cornea.2011，30(10):1098-1104.
[20] Avunduk AM, Avunduk MC, Varnell ED, et al. The comparison of efficacies oftopical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: aclinical and immunocytochemical study[J]. Am. J. Opthalmol.2003，136(4):593-602.
[21] Pflugfelder SC，Maskin Sl，Anderson B，et al. A randomized, double-masked,placebo-controlled, multicenter comparsion of loteprednol etabonate ophthalmicsuspension,0.5%, and placebo for treatment of keratoconjunctivitis sicca in patientswith delayed tear clearance[J]. Am. J. Opthalmol.2004，138(8):444-457.
[22]Avunduk AM，Avunduk MC，Varnell ED，et al. The comparison of efficacies oftopical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: aclinical and immunocytochemical study[J]. Am J Ophthalmol.2003，136(4):593-602.
[23] Lee HK，Ryu IH，Seo KY，et al. Topical0.1%Prednisolone Lowers Nerve GrowthFactor Expression in Keratoconjunctivitis Sicca Patients[J]. Opthalmology.2006，113(2):198-205.
[24] Fox RI，Chan R，Michelson JB，et al. Beneficial effect of artificial tears made withautologous serum in patients with keratoconjunctivitis sicca[J]. Arthritis Rheu.1984，27(4):459-461.
[25] Kojima T，Ishida R，Dogru M，et al. The effect of autologous serum eye drops in thetreatment of severe dry eye disease: a prospective randomized case-control study[J].Am J Ophthalmol.2005，139(3):242-246.
[26] Lo′pez-Plandolit S，Morales MC，Freire V，et al. Efficacy of Plasma Rich in GrowthFactors for the Treatment of Dry Eye[J]. Cornea.2011，30(12):1312-1317.
[27] Rocha G，Acera A，Dura′n JA. Laser in situ keratomileusis flap necrosis aftertrigeminal nerve palsy[J]. Arch Ophthalmol.2007，125(10):1423-1425.
[28] Lo′pez-Plandolit S, Morales MC, Freire V, et al. Plasma rich in growth factors (PRGF)as a therapeutic agent for severe persistent corneal epithelial defects[J]. Cornea.2010，29(8):843-848.
[29] Matta JA， Miyares RL， Ahern GA. TRPV1is a novel target for omega-3polyunsaturated fatty acids[J]. J Physiology.2007，578(pt2):397-411.
[30] Xu ZZ，Zhang L，Liu T，et al. Resolvins RvE1and RvD1attenuate inflammatorypain via central and peripheral actions[J]. Nature Med.2010，16(5):592-597.
[31] Serhan CN. Systems approach with inflammatory exudates uncovers novelanti-inflammatory and pro-resolving mediators[J]. Prostaglandins Leukot Essent FattyAcids.2008，79(3-5):157-163.
[32] Aragona P，Bucolo C，Spinella R，et al. Systemic omega-6essential fatty acidtreatment and pge1tear content in Sjogren’s syndrome patients[J]. Invest OphthalmolVis Sci.2005，46(12):4474-4479.
[33] Kokke KH，Morris JA，Lawrenson JG. Oral omega-6essential fatty acid treatment incontact lens associated dry eye[J]. Cont Lens Anterior Eye.2008，31(3):141-146.
[34] Creuzot C，Passemard M，Viau S，et al. Improvement of dry eye symptoms withpolyunsaturated fatty acids[J]. J Fr Ophtalmol.2006，29(8):868-873.
[35] de Paiva CS， Schwartz CZ，Gj rstrup P，et al. Resolvin E1(RX-10001) ReducesCorneal Epithelial Barrier Disruption and Protects Against Goblet Cell Loss in aMurine Model of Dry Eye[J]. Cornea.2012，Jan17.
[36] Ja¨rvinen RL，Larmo PS，Seta¨la¨ NL，et al. Effects of Oral Sea Buckthorn Oil on TearFilm Fatty Acids in Individuals With Dry Eye[J]. Cornea.2011，30(9):1013-1019.
[37] Kokke KH，Morris JA，Lawrenson JG. Oral omega-6essential fatty acid treatment incontact lens associated dry eye[J]. Cont Lens Anterior Eye.2008，31(3):141-146.
[38] Ono M，Rocha FJ，Sullivan DA，et al. Immunocytochemical location and hormonalcontrol of androgen receptors in lacrimal tissues of the female MRL/Mp-lpr/lpr mousemodel of sjogren’s syndrome[J]. Exp Eye Res.1995，61(6):659-666.
[39] Sullivan DA，Jensen RV，Suzuki T，et al. Do sex steroids exert sex-specific and/oropposite effects on gene expression in lacrimal and meibomian glands?[J]. Mol vis.2009，15(10):1553-1572.
[40]赫凤芹，张明昌，姜发纲.性激素受体在人眼角膜组织中的表达[J].临床眼科杂志.2005，13(3):274-276.
[41] Krenzer KL，Dana MR，Ullman MD，et al. Effects of androgen deficiency on thehuman meibomian gland and ocular surface[J]. J clin Endocrinol Metab.2000，85(12):4874-4882.
[42] Sullivan DA，Krenzer KL，Sullivan BD，et al. Does androgen insufficiency causelacrimal gland inflammation and aqueous tear deficiency?[J]. Invest. Ophthalmol.Vis. Sci.1999，40(6):1261-1265.
[43] Worda C，Nepp J，Huber JC，et al. Treatment of keratoconjunctivitis sicca with topicalandrogen[J]. Maturitas.2001，37(3):209-212.
[44] Deshande A，Heller J，Gurny R. Bioerodible polymers for ocular delivery[J]. Crit. Rev.Ther. Drug Carrier Syst.1998，15(4):381-420.
[45] Calvo P，Sanchez A，Marta-nez J，et al. Polyester nanocapsules as new topical oculardelivery systems for cyclosporin A[J]. Pharmaceutical Research.1996，13(2):311-315.
[46] De Campos AM，Sanchez A，Alonso MJ. Chitosan nanparticles: a new vehicle for theimprovement of the delivery of drugs to the ocular surface. Application to cyclosporinA[J]. Int. J. Pharm.2001，224(1-2):159-168.
[47] Goto E，Yagi Y，Kaido M，et al. Improved functional visual acuity after punctalocclusion in dry eye patients[J]. Am J Ophthalmol.2003，135(5):704-705.
[48] Benson DR，Hemmady PB，Snyder RW，et al. Efficacy of laser punctal occlusion[J].Ophthalmology.1992，99(4):618-621.
[49] McDonald M，D'Aversa G，Perry HD，et al. Hydroxypropyl cellulose ophthalmicinserts (lacrisert) reduce the signs and symptoms of dry eye syndrome and improvepatient quality of life[J]. Trans. Am. Ophthalmol. Soc.2009，107:214-221.
[50] Geerling G，Sieg P. Transplantation of the major salivary glands[J]. Dev. Ophthalmol.2008，41:255-268.
[51] Lane SS，DuBiner HB，Epstein RJ，et al. A New System, the LipiFlow, for theTreatment of Meibomian Gland Dysfunction (MGD)[J]. Cornea.2012，Jan4.
[52] Blom M，Kopp S，Lundeberg T. Prognostic value of the pilocarpine test to identifypatients who may obtain long-term relief from xerostomia by acupuncturetreatment[J]. Arch. Otolaryngol. Head Neck Surg.1999，125(5):561-566.
[53] Nepp J，Derbolav A，Haslinger-Akramian J，et al. Effects of acupuncture inkeratoconjunctivitis sicca[J]. Klin. Monatsbl. Augenheilked.1999，215(4):228-232.