角膜新生血管化

摘要： 目的 评价雷珠单抗治疗老年人角膜新生血管(CNV)的临床疗效和安全性. 方法 共纳入CNV老年患者40例(50只眼),以2015年1-12月的20例患者(22只眼)为观察组,给予结膜下注射雷珠单抗治疗;以2014年6-12月的20例患者(28只眼)为对照组,给予激光光凝术治疗;比较两组患者治疗前和治疗后1个月、6个月和12个月视力、CNV面积、眼压和治疗有效率,治疗后随访12个月记录患者有无复发和并发症情况. 结果 治疗后1个月,观察组视力测试提高1行以上者为20只眼(90.9％),明显高于对照组16只眼(57.1％)(x2=6.910、P=0.031);治疗后6个月,观察组视力测试提高1行以上者为19只眼(86.3％),明显高于对照组14只眼(50.0％)(x2=5.866、P=0.020);治疗后12个月,观察组视力测试提高1行以上者为19只眼(86.3％),明显高于对照组12只眼(42.9％)(x2=8.010、P=0.016).观察组和对照组治疗后CNV面积均较治疗前减少,且观察组治疗后1个月、6个月和12个月CNV面积均明显小于对照组,差异均有统计学意义(t=6.109、5.291、＆330,P=0.019、0.033、0.009).观察组和对照组治疗前后眼压变化差异无统计学意义(均P＞0.05).观察组治疗有效率为90.9％(20/22),明显高于对照组75.0％ (21/28)(x2=6.109、P=0.006).术后随访12个月结果显示,对照组中有7只眼(25.0％)出现新生血管复发,明显高于观察组2只眼(9.1％)(x2 =8.668、P=0.003). 结论 结膜下注射雷珠单抗治疗老年人CNV安全有效,并发症少,可在临床上推广应用.%Objective To evaluate the clinical efficacy and safety of ranibizumab in the treatment of corneal neovascularization(CNV)in elderly patients.Methods A total of 40 elderly patients(50 eyes)with conceal neovascularization were enrolled in this study at our hospital.Among them,20 patients(22 eyes)in observation group enrolled from January 2015 to December 2015,received subconjunctival injection of ranibizumab,and 20 patients(28 eyes)in control group enrolled from June 2014 to December 2014,receivedlaser photocoagulation.The visual acuity,the area of corneal neovascularization,intraocular pressure and therapeutic response rate were measured and compared between two groups before and 1 month,6 months and 12 months after treatment.All patients were followed up for 12 months to record the recurrence and complications.Results In the observation group,20 eyes(90.9％),19 eyes(86.3 ％)and 19 eyes(86.3％)got an improved eyesight at 1 month,6 months and 12 months of ranibizumab treatment,respectively,which were significantly higher than those in the control group(16/57.1％,14/50.0％,12/42.9％,x2 =6.910,5.866,8.010;P=0.031,0.020,0.016,respectively).The area of corneal neovascularization was decreased in both groups after treatment in the comparison of pretreatment.What is more important:at 1 month,6 months and 12 months of treatment,the areas of CNV were all significantly smaller in the observation group than in the control group (t =6.109,5.291,8.330;P =0.019,0.033,0.009,respectively).There was no significant difference in intraocular pressure before versus after treatment in both groups(both P＞ 0.05).The therapeutic response rate was 90.9% (20/22)in observation group,and 75.0% (21/28)in control group(x2 =6.109,P =0.006).During the 12-month follow-up after operation,the recurrence rate of CNV was significantly higher in control group(7 eyes,25.0％)than in observation group(2 eyes,9.1%) (x2 =8.668,P =0.003).Conclusions Subconjunctival injection of ranibizumab is effective and safe with a fewer complications in the treatment of corneal neovascularization in elderly patients,which is worthy of generalizing in clinical treatments.

摘要： Objective To observe the changes that occur as a rule in microRNA-21 (miR-21) expression in a mouse corneal neovascularization (CorNV) model induced by alkali burn and its relationship with vascular endothelial growth factor-A (VEGF-A).Methods This was an experimental study.All right eyes of sixty-eight BALB/c mice were used to create models of CorNV induced by alkali burn and were included as the experimental group;the untreated left eyes were included as the control group.Biomicroscopic neovascularization was observed and photographed on days 4, 7, 14, 21 and 28.The areas of CorNV were then calculated.On days 4, 7, 14, 28 after alkali-induced injury, 3 mice were randomly euthanized and six eye balls were embedded in paraffin.Sections were cut for hematoxylin-eosin (HE) staining and immunohistochemical (IHC) staining to observe the corneal histopathological changes and to detect the protein expression of VEGF-A.Fourteen mice were randomly sacrificed for testing the expression of miR-21 and VEGF-A mRNA in corneal tissues by quantitative real-time polymerase chain reaction (real-time PCR).The results were analyzed statistically with an analysis of variance of repeated measurement data.Linear correlation analysis was used for correlation analysis.Results After alkali-induced injury, slit lamp biomicroscopy was used to detect CorNV.It was first detected on day 4, peaked on day 14, and started to regress after day 21.The maximum area of CorNV appeared on day 14.HE staining showed that CorNV was most obvious on day 14 after alkali injury and less obvious on day 28.IHC showed that expression of VEGF-A positive staining was higher than in the control group (t=19.47,61.8, 44.18, P＜0.05) on days 4, 7, 14.Positive staining of VEGF-A was obvious on day 7 and started to decrease after day 14.The difference was statistically significant (F=649.4, P＜0.05).Real-time PCR analysis showed that on days 4, 7, 14, 28 after injury, the relative expression of miR-21 increased in the alkali-burn group compared to the control group (t=4.60, 14.74, 9.78, 5.69, P＜0.01) and VEGF-A mRNA levels were higher than levels in the control group on days 4, 7, 14 after injury (t=5.82, 14.11, 3.41, P＜0.05).Their expression levels both reached a maximum on day 7 (F=62.1, 64.5, P＜0.05).There were positive correlations in miR-21 expression with VEGF-A mRNA and VEGF protein at each investigative time point (r=0.62 and r=0.66, respectively, P＜0.05).Conclusion miR-21 and VEGF-A were upregulated during the CorNV course in a mouse model induced by alkali burn.The peak expression of miR-21, VEGF-A mRNA and protein preceded CorNV formation.miR-21 may play a potential role through the VEGF signal pathway in the course of CorNV formation.%目的 观察microRNA-21 (miR-21)在碱烧伤诱导小鼠角膜新生血管(CorNV)模型中的变化规律及其与血管内皮生长因子-A(VEGF-A)的关系.方法 实验研究.68只BALB/c小鼠,右眼制备碱烧伤诱导CorNV模型作为实验组,左眼作为正常对照组不予任何处理.碱烧伤后第4、7、14、21、28天行眼前节照相测量CorNV面积.分别在碱烧伤后第4、7、14、28天分别随机处死3只小鼠取眼球制石蜡切片,通过苏木素-伊红(HE)染色观察角膜的组织病理学改变,免疫组织化学(IHC)染色检测角膜VEGF-A表达;各时间点随机处死14只小鼠行实时荧光定量聚合酶链式反应(Real-time PCR)检测角膜miR-21及VEGF-A mRNA的表达.数据分析采用单因素方差分析、配对样本t检验、直线相关分析.结果 小鼠CorNV于碱烧伤后第4天开始出现,14天时生长达高峰,21天后逐渐消退.HE染色显示实验组角膜第14天呈现较多粗大CorNV,28天时明显减少.同期IHC染色显示实验组角膜在第4、7、14天时VEGF-A阳性表达均高于对照组(t=19.47、61.86、44.18,P＜0.05),28天时差异无统计学意义(t=2.52,P＞0.05).实验组第7天时角膜VEGF-A阳性表达明显,14天后表达相对减弱,差异具有统计学意义(F=649.4,P＜0.05).实验组角膜在第4、7、14、28天时miR-21表达均高于对照组(t=4.60、14.74、9.78、5.69,P＜0.01);VEGF-A mRNA实验组角膜在第4、7、14天时高于对照组(t=5.82、14.11、3.41,P＜0.05),28天时差异无统计学意义(t=0.76,P＞0.05);且两者表达均于第7天时达高峰,差异均具有统计学意义(F=62.1、64.5,P＜0.05).miR-21与VEGF-A mRNA及其蛋白表达均呈正相关(r=0.62、0.66,P＜0.05).结论 碱烧伤诱导小鼠角膜CorNV形成中miR-21、VEGF-A表达均升高,且miR-21、VEGF-A mRNA和蛋白表达高峰较CorNV形成高峰早,提示miR-21可能通过VEGF信号通路参与CorNV形成.

摘要： The studies and clinical applications of Ranibizumab and Bevacizumab which are new anti-VEGF drugs have made significant progression on the treatment of corneal neovascularization.The effectiveness and safety of Ranibizumab compared with Bevacizumab has been the focus of the debate for scholars nowadays.Some experiments showed that the effect of Bevacizumab was better than Ranibizumab.But combined with our experiments, Ranibizumab represented the advantages of shorter effect time, stronger affinity with VEGF-A, better tolerance with repeated injections etc.So we believed that the adequate doses of ranibizumab had better effects.Its clinical application should be paid much attention.%在治疗角膜新生血管方面,以雷珠单抗和贝伐单抗为代表的新型抗VEGF药物的临床应用及研究均取得重大突破,而二者的有效性及安全性比较是当前临床争议的焦点.虽然部分实验结果表明贝伐单抗的药效优于雷珠单抗,但是雷珠单抗具有起效时间短、对VEGF-A的亲和力强、重复注射时耐受性好等优点.结合实验研究结果,我们认为充足剂量的雷珠单抗效果更优,其临床应用应引起广泛重视.

摘要： AlM: To explore the inhibiting effect of FTY720 on corneal neovascularization ( CNV) of rat.METHODS: MTT assay and cells scratch were adopted to observe hyperplasia of human umbilical vein endothelial cells ( HUVECs ) and cell migration induced by sphingosine-1-phosphate(S1P) after using FTY720 of different concentration. The effect of FTY720 on CNV induced by S1P in a rat corneal micropocket model was detected. 30SD rats were randomly divided into group A, group B and group C with 10 rats per group. S1P and 0μg, 5μg, and 20μg FTY720 controlled-released particles were implanted into the corneal stroma. The growth of CNV and having pathological examination on 12d after the operation was observed. Findings was analyzed by one-way ANOVA.RESULTS: 10, 102 , 103 , and 104 nmol/L FTY720 and HUVECs co-incubate 72h could inhibit cell proliferation (P < 0. 01 ), 24h after the function of 10, 100nmol/L FTY720, it could inhibit S1P-induced cell migration and the ability of restricting cell proliferation and cell migration was enhanced with increasing concentration of FTY720. On 12d, after rat corneal micropocket controlled-release particles was implanted into groups A, B, C, the CNV area were respectively 10. 05±1. 19, 6. 59±0. 95, 2. 70± 0.68mm2(F=145. 155, P<0. 01), group A and group B was statistically different and this was the same case between group B and group C (P<0. 01).CONCLUSlON:FTY720 can inhibit S1P-induced corneal neovascularization.%目的：：探讨芬戈莫德(fingolimod,FTY720)对大鼠角膜新生血管( CNV)的抑制作用。方法：分别采用MTT法和划痕法观察不同浓度FTY720对人脐静脉内皮细胞( HUVECs )的增生和S1 P诱导下的细胞迁移的影响。应用大鼠角膜微囊袋模型,检测FTY720对S1 P诱导的CNV的作用。将30只SD大鼠按随机数字表法分成A、B和C组,每组10只,在各组角膜基质层内植入S1 P的同时依次植入0,5,20μg FTY720缓释颗粒。术后对CNV生长情况观察,并在12 d行组织病理学检查。实验结果采用单因素方差分析。结果：10,102,103,104 nmol/L FTY720与HUVECs共孵育72h可抑制细胞增生(P<0.01),10,100nmol/L FTY720作用24 h后,可抑制由S1 P诱导的细胞迁移,随FTY720浓度增加其抑制细胞增生和迁移的作用均增强,A、B、C组大鼠角膜微囊袋缓释微粒体植入后12d,CNV面积分别为10.05±1.19,6.59±0.95,2.70±0.68mm2(F=145.155, P<0.01),A与B组、B与C组间均有统计学差异(P<0.01)。

摘要： Objective:To evaluate the efficacy of epigallocatechin gallate ( EGCG) in treatment of corneal alkali burn injury in mice .Methods:Corneal alkali burn injury was induced by sodium hydroxide method in C 57BL/6J mice.The mice with cornea burns were treated intraperitoneally with EGCG solution or phosphate buffer solution ( PBS ) respectively . The healing of corneal epithelium , the formation of corneal neovascularization ( CNV ) and the inflammation reaction were assessed by slit-lamp microscopy and histological examination . Expression of vascular endothelial growth factor ( VEGF ) mRNA and protein in cornea was evaluated by real-time reverse transcription polymerase chain reaction ( RT-PCR ) and immunohistochemistry , respectively .Myeloperoxidase ( MPO ) assay was used to quantitatively evaluate the polymorphonuclear neutrophils ( PMNs ) infiltration in the corneas . Results: The healing rate of corneal epithelium in EGCG group was significantly higher than that of PBS group at d1, d3 and d7 after treatment ( d1: 41.0% ±13.0% vs 23.8% ± 7.6%;d3:76.6%±7.5% vs 61.2%±6.8%; d7: 87.8%±8.5% vs 74.0%± 9.1%;all P <0.05 ) .The CNV scores and the number of CNV in the corneal sections of EGCG group were significantly lower than those of PBS group at d 3 , d7 and d14 after treatment ( CNV score: d3: 1.1 ±0.5 vs 6.6 ±1.0; d7: 1.3 ±0.3 vs 8.1 ±1.0;d14:0.9 ±0.2 vs 9.2 ±1.1; CNV number: d3:1.68 ±0.61 vs 2.92 ±0.95; d7:4.80 ±1.36 vs 7.92 ±1.28;d14:3.64 ±0.71 vs 5.88 ±0.76;all P <0.05 ) .The expression of VEGF protein at d3 (0.19 ±0.05 vs 0.45 ±0.08) and d7 (0.42 ±0.07 vs 0.84 ±0.09 ) , the expression of VEGF mRNA at d 1 , d3 and d7 in EGCG group were significantly lower than those in PBS group ( all P <0.05 ) .Compared to PBS group, the inflammatory index at d3 (3.2 ±0.4 vs 3.7 ±0.5) and d7 (2.3 ±0.5 vs 4.0 ±0.0 ) , the number of PMNs in the corneal sections and the MPO values at d 3 , d7 and d14 in EGCG group were significantly decreased ( PMNs: d3: 34.5 ±15.7 vs 90.0 ±28.8;d7:17.1 ±11.4 vs 54.9 ±25.9;d14:12.8 ±4.6 vs 39.0 ±17.9; all P <0.05 ) .Conclusion: In the murine corneal alkali burn model , intraperitoneal injection of EGCG solution can promote the healing of corneal epithelium , inhibit the formation of CNV and reduce the inflammatory cell infiltration in the corneas .%目的：研究表没食子儿茶素没食子酸酯（EGCG）对角膜碱烧伤的治疗作用。方法：制作C57BL／6J小鼠角膜碱烧伤模型，实验分为EGCG组和磷酸盐缓冲液（ PBS）组，分别给予腹腔注射EGCG溶液或者等量PBS，裂隙灯显微镜和组织病理学观察和评价小鼠角膜上皮修复、新生血管生长以及炎症反应程度，免疫组织化学染色和实时定量PCR法检测血管内皮生长因子（ VEGF）的表达，髓过氧化物酶定量测定评价中性粒细胞的浸润程度。结果：EGCG组小鼠角膜上皮修复速率显著大于PBS组，碱烧伤后第1、3、7天的差异有统计学意义（均P＜0．05）。EGCG组和PBS组小鼠均见新生血管生长，在碱烧伤后第3、7、14天EGCG组新生血管评分和角膜切片中新生血管数量均显著低于PBS组， EGCG组的VEGF蛋白表达量在碱烧伤后第3、7天显著低于PBS组，EGCG组VEGFmRNA表达量在碱烧伤后第1、3、7天均低于PBS组，差异均有统计学意义（均P＜0．05）。碱烧伤后第7、14天EGCG组的炎症指数低于PBS组，第3、7、14天EGCG组角膜组织切片中中性粒细胞浸润数量和髓过氧化物酶检测值均低于PBS组，差异均有统计学意义（均P＜0．05）。结论：腹腔注射EGCG可有效促进碱烧伤后小鼠角膜上皮修复，抑制新生血管形成和炎症细胞浸润。

摘要： 目的 探讨趋化因子受体CCR3拮抗剂在实验性角膜新生血管发生过程中的作用及机制.方法 实验研究.以碱烧伤法诱导实验性小鼠角膜新生血管模型;选用动物为54只7～8周龄雄性健康的BABL/c小鼠,随机数字表法分成对照组、实验组及VEGF抗体阳性对照组,每组18只;Real-time PCR法检测CCR3在碱烧伤角膜组织中的动态表达;烧伤后角膜局部应用CCR拮抗剂进行干预,在碱烧伤后2周大体观察及全角膜铺片CD31组织化学染色法检测角膜新生血管发生情况;Real-time PCR和免疫印迹法检测烧伤角膜组织内血管生成相关因子的表达.应用独立样本t检验法比较各组间差异.结果 碱烧伤后2周,CCR3拮抗剂干预组角膜新生血管相对值较对照组明显减少.对照组为0.77 ±0.15,实验组为0.51 ±0.03,差异有统计学意义(￡=12.91,P =0.00).免疫印迹检测结果显示角膜组织内VEGF的表达对照组为1.15 ±0.30,实验组为0.91 ±0.24,差异无统计学意义(t=1.08,P =0.34).结论 CCR3信号通路阻滞后能抑制实验性角膜新生血管的发生.%Objective To explore the effect of CCR3 antagonist on the development of experimental corneal neovascularization.Methods Mouse corneas were burned by NaOH to induce corneal neovascularization.Fifty four clean male BABL/c mice aged 7-8 weeks were divided into control group,CCR3 antagonist group and VEGF antibody positive group according to randomized number table.The gene expression of CCR3 and its ligand eotaxin in burned corneas was examined by Real-time PCR.CCR3 antagonist was locally administrated after alkali injury and the formation of corneal neovascular 2 weeks after injury was examined using a digital camera linked to a slit lamp microscope and corneal whole mount staining with CD31.The mRNA and protein expression of chemokines in burned corneas was detected by Real-time PCR and western blot.Results Compared to control group,CCR3 antagonist treated mice resulted in significantly decreased corneal neovascularization.The related CNV area was 0.51 ± 0.03 in the CCR3 antagonist group,and that in the control group was 0.77 ± 0.15,with significant difference between them (t =12.91,P =0.00).Western blot detection did not show significant difference of VEGF protein expression between two groups.Expression level of VEGF in the CCR3 antagonist group was 0.91 ± 0.24,and that in the control group was 1.15 ± 0.30,showing no significant difference (t =1.08,P =0.34).Conclusions Alkali-induced corneal neovascularization was inhibited by CCR3 antagonist.The mechanism that CCR3 pathway plays an important role in corneal neovascularization needs further exploration.

摘要： 角膜新生血管(CNV)是角膜疾病中一种常见的病理性改变,也是导致视力下降的重要原因.目前研究表明,CNV的发生与血管内皮生长因子(VEGF)等的调控表达密切相关,随着抗VEGF药物的研究及其在临床中的应用,其在治疗由角膜疾病引起的CNV这一病理过程中将会产生不可忽视的作用.该文对抗VEGF药物治疗CNV性疾病的几种方法进行综述.

摘要： 目的：探讨无缝线骨髓间充质干细胞（bonemarrowmesenchymestemcells，BMMSCs）羊膜移植在兔角膜缘干细胞缺损模型的应用效果。方法选择新西兰白兔36只（72眼），制作兔角膜缘干细胞缺损模型第7天随机分为两组：实验组进行无缝线BMMSCs羊膜移植术组，对照组进行单纯羊膜移植术。分别于术后1、2、3、7、14、28d观察眼压情况、角膜新生血管、角膜透明度、前房反应及泪液分泌情况，术后1周和1个月每组各处死3只兔，摘除眼球，12眼（两组各6眼）作病理切片检查，HE染色观察比较炎症细胞和角膜上皮细胞形态并进行细胞计数。结果裂隙灯检查眼压、前房反应和并发症在组间各时间点差异无显著性（P均＞0.05）。而术后1个月泪液分泌、角膜新生血管和透明度组间比较差异有统计学意义（tCNV＝5.692，tCT＝6.316，tST＝9.197，P均＜0.05），HE显示两组角膜上皮数有显著性差异（t＝7.287，P＜0.05），炎症细胞数也有显著性差异（t＝9.178，P＜0.05）。结论无缝线BMMSCs羊膜移植应用于兔角膜新生血管中炎症反应小，泪液分泌影响少，角膜透明度高。

摘要： 本发明属于生物医用材料与医学交叉领域，具体公开一种雷公藤红素在制备抑制碱烧伤角膜新生血管及促进角膜碱烧伤愈合滴眼液制剂中的应用。称取三元嵌段共聚物PEG‑PCL‑PEI7.04~67.55 g、雷公藤红素0.68~2.11 g，共同溶解于由甲醇与乙腈以体积比1:1~3组成的混合溶剂中；然后，在超声搅拌下，将混合液滴加到溶解当量的注射用水中，真空蒸馏除去有机溶剂，超滤除去游离的雷公藤红素，得载药聚合物胶束，补加注射用水定容至100mL，即得滴眼液。本发明首次以PEG‑PCL‑PEI为载体，负载雷公藤红素，制成了滴眼液，实现眼表点眼的给药方式，具有里程碑式的意义。

摘要： 本发明公开了一种用于治疗非感染性眼部炎症、抑制角膜新生血管形成和角膜移植后抗排异反应的配方，通过等渗剂、缓冲剂的选择，防腐剂、释微球制剂、重组人白细胞介素-8受体拮抗剂和趋化素样因子1(CKLF1)的添加，增加了重组人白细胞介素-1受体拮抗剂的活性，延长了其保存时间。解决了现有技术中重组人白细胞介素-1受体拮抗剂对外部环境要求较高，容易失活的问题，并通过添加重组人白细胞介素-8受体拮抗剂和趋化素样因子1与重组人白细胞介素-1受体拮抗剂之间产生协同效应，来减少用量。

摘要： 本发明公开了一种两亲性氟硼染料有机物及其制备和在抑制眼角膜新生血管生长光敏药物中的应用。基于经典的氟硼染料合成路线及Knoevenagel等有机反应合成一系列两亲性氟硼染料有机物，该两亲性氟硼染料有机物在水溶液中可以组装形成1～100纳米的纳米粒子，能成功穿透细胞膜进入细胞中，且在680nm光照条件下，能产生单线态氧，从而抑制眼角膜新生血管的生长，适用于角膜新生血管生长的光动力学治疗。

摘要： 本发明属于生物医用材料与医学交叉领域，具体公开一种雷公藤红素在制备抑制碱烧伤角膜新生血管及促进角膜碱烧伤愈合滴眼液制剂中的应用。称取三元嵌段共聚物PEG‑PCL‑PEI 7.04~67.55 g、雷公藤红素0.68~2.11 g，共同溶解于由甲醇与乙腈以体积比1:1~3组成的混合溶剂中；然后，在超声搅拌下，将混合液滴加到溶解当量的注射用水中，真空蒸馏除去有机溶剂，超滤除去游离的雷公藤红素，得载药聚合物胶束，补加注射用水定容至100mL，即得滴眼液。本发明首次以PEG‑PCL‑PEI为载体，负载雷公藤红素，制成了滴眼液，实现眼表点眼的给药方式，具有里程碑式的意义。

摘要： 本发明公开了一种用于治疗非感染性眼部炎症、抑制角膜新生血管形成和角膜移植后抗排异反应的配方，通过等渗剂、缓冲剂的选择，防腐剂、释微球制剂、重组人白细胞介素-8受体拮抗剂和趋化素样因子1(CKLF1)的添加，增加了重组人白细胞介素-1受体拮抗剂的活性，延长了其保存时间。解决了现有技术中重组人白细胞介素-1受体拮抗剂对外部环境要求较高，容易失活的问题，并通过添加重组人白细胞介素-8受体拮抗剂和趋化素样因子1与重组人白细胞介素-1受体拮抗剂之间产生协同效应，来减少用量。

摘要： 本发明涉及抗PDL1抗体在用于治疗角膜新生血管性疾病中的应用。本发明通过构建碱烧伤诱导的角膜新生血管动物模型，通过局部应用抗PDL1抗体后进行裂隙灯检查评估角膜新生血管、角膜血管组织免疫荧光染色等实验发现，抗PDL1抗体治疗组小鼠的角膜新生血管明显减少，说明局部应用抗PDL1抗体可抑制角膜新生血管。证实抗了PDL1抗体可显著减少PDL1hiCXCR2low中性粒细胞亚群的浸润，抑制其分泌的一系列炎症因子和血管生长因子，从而发挥抑制病理性新生血管的作用。本发明为抗PDL1抗体治疗角膜新生血管性疾病及拓展抗PDL1抗体的临床应用提供实验依据和理论基础，揭示抗PDL1抗体在新生血管性疾病领域具有明确的临床应用前景。

摘要： 本发明属于眼部药品制备技术领域。针对目前角膜新生血管的预防与治疗手段会引发并发症的问题，本发明提供CB‑839在制备抑制角膜新生血管生成的药物中的应用。本发明通过负载CB‑839的药物能够明显抑制小鼠角膜新生血管生成，炎症细胞浸润减少，并且没有发现明显副作用，弥补了现有技术的不足。

摘要： 本发明提供了一种角膜新生血管动物模型及其构建方法，该动物模型包括在小鼠的角膜中央切口，并在角膜缘的正前方做潜行隧道，将含血管内皮生长因子的滤纸植入隧道顶端，构建得到角膜新生血管动物模型；在小鼠的角膜中央切口之前，用戊巴比妥钠溶液注射小鼠的腹腔，爱尔凯因滴眼液麻醉小鼠的双眼表面；本发明的滤纸较薄、制作时间短，易于手术过程中植入，造模成功率高，从而增加了造模的可重复性，大大降低了成本的投入；本发明使用滤纸结合血管生长因子植入小鼠角膜层间，诱导小鼠角膜新生血管模型，可用于小鼠角膜，具有造模时间短、成本低、创伤小、且可重复性高的特点，为研究角膜新生血管抑制剂提供稳定、可靠的模型体系。

摘要： 本发明提供了一种角膜新生血管/淋巴管生成损伤模型及其构建方法和应用。其中，该模型是在角膜缝线的思路基础上，采用角膜上皮机械刮除联合生物胶黏合角膜缝线于角膜基质的方式构建得到，这样既解决了角膜缝线模型应用在小型啮齿类动物时造模难度大、效率低的问题，又避免了角膜穿孔、缝线脱落等导致造模失败的常见原因，还保留了角膜缝线新生血管生长比较规则、避免化学诱导方法中化学试剂影响、损伤方式单一可控等优点。此外，基于该模型的构建方法，能够简便、有效、可控的作为小鼠、大鼠角膜新生血管或淋巴管生成的一种新型有效模型，因而，其适用性较强。

摘要： 本发明公开了TIR/BB环拟似物AS‑1在制备治疗角膜新生血管性疾病的药物中的应用，特别是制备治疗角膜碱烧伤的药物中的应用。本发明首次将脂溶性小分子多肽引入角膜碱烧伤的治疗领域，对AS‑1对角膜碱烧伤治疗作用的研究，不仅为碱烧伤角膜新生血管和角膜新生淋巴管的治疗提供新的靶向药物，同时为小分子多肽治疗角膜碱烧伤提供新思路。