Expression of MMP, HPSE, and FAP in Stroma Promoted Corneal Neovascularization Induced by Different Etiological Factors
Expression of MMP, HPSE, and FAP in Stroma Promoted Corneal Neovascularization Induced by Different Etiological Factors
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DOI：
10.3109/02713683.2010.502294
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发表时间：
2010-10
影响因子：
2
通讯作者：
W. Shi;Juncai Liu;Man Li;Hua Gao;Ting Wang
中科院分区：
文献类型：
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作者：
W. Shi;Juncai Liu;Man Li;Hua Gao;Ting Wang
目的：观察基质金属蛋白酶（MMP-2、MMP-9）、乙酰肝素酶（HPSE）、成纤维细胞活化蛋白（FAP）的表达与不同病因诱导的角膜新生血管形成的关系。方法：建立碱烧伤、真菌感染、真菌感染、免疫原植入和肿瘤细胞植入5种动物模型。裂隙灯下观察各模型角膜新生血管的长入时间和形态。组织病理学检查角膜基质中的炎症和新生血管。MMP-2、MMP-9、HPSE、FAP采用免疫组化或免疫荧光双标法检测。结果：各模型角膜新生血管均从第3天开始侵入角膜。角膜新生血管在碱烧伤模型、真菌感染模型和角膜溃疡模型中分别呈树枝状、刷状和三角形，后两种模型均到达角膜中央。各模型第1天间质内出现炎性细胞，第3天起间质内有新生血管生长，第3-14天两者相伴出现。MMP-2、MMP-9和HPSE在新生血管形成前第1天出现，并伴随新生血管形成3-14天。FAP+细胞主要分布在CD 31+血管内皮细胞周围。结论：不同病因引起的角膜新生血管形态不同。基质中的炎症反应和MMP、HPSE、FAP的表达可能是角膜新生血管生长的先导。
Purpose: To observe the relationship between the expression of matrix metalloproteinases (MMP-2, MMP-9), heparanase (HPSE), and fibroblast activation protein (FAP) in stroma and corneal neovascularization induced by different etiological factors. Methods: Five models were established: alkaline burn, fungal infection, suturing, immunogen implantation, and tumor cell implantation. The ingrowth time and morphology of corneal neovascularization in each model was observed by slit lamp. Inflammation and neovascularization in the corneal stroma were examined by histopathology. MMP-2, MMP-9, HPSE, and FAP were detected by immunohistochemistry or double immunofluorescence staining. Results: The neovascular vessels started to invade the cornea from the third day in each model. The corneal neovascularization presented dendritic-form, brush-form, and triangle-form in alkaline burn, fungal infection, and suturing models, respectively, and reached to the central cornea in the latter two models. The inflammatory cells appeared in the stroma on the first day, while neovascular vessels grew into the stroma from the third day and both of them accompanied each other from 3–14 days in each model. MMP-2, MMP-9, and HPSE appeared before the neovascularization on the first day and accompanied it from 3–14 days in each model. FAP+ cells occurred mainly around CD31+ vascular endothelial cells in each model. Conclusion: The corneal neovascularization induced by different etiological factors have different morphologies. The inflammation and the expression of MMP, HPSE, and FAP in stroma may serve as pioneers for the growth of corneal neovascularization.