Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, Chicago, IL, USA.
Cornea. 2012 Jan;31(1):74-80. doi: 10.1097/ICO.0b013e31821dd986.
We characterized the presence of hemangiogenesis (HA) and lymphangiogenesis (LA) in human corneal specimens exhibiting 13 underlying pathologies.
Human corneal specimens were obtained from consenting subjects (n = 2 or n = 3 for each pathology; total sample size, n = 35). The pathological specimens were stained with hematoxylin and eosin (H&E) to determine the presence or absence of corneal neovascularization (NV) and superficial or deep stromal distribution of NV. Immunohistochemical staining was then performed to differentiate HA (positive for CD31) from LA (positive for lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1]).
The double-negative (CD31(-)/LYVE-1(-)) immunostaining, indicating the absence of NV, was exhibited by 21 specimens (60%). CD31(-)/LYVE-1(-), indicating the presence of HA and absence of LA, was exhibited by 12 specimens (34%). The double-positive (CD31(+)/LYVE-1(+)) phenotype, indicating both HA and LA, was exhibited by 2 specimens (6%). Notably, the CD31(-)/LYVE-1(-) phenotype, indicating the presence of LA and absence of HA, was not detected among the specimens. Deep stromal NV was exhibited in a 4:3 ratio to superficial stromal NV. The double-negative immunostaining was more prevalent in noninflammatory pathologies, particularly in comparison with combined neovascular phenotypes (ie, CD31(+) or LYVE-1(+)). Among the neovascular phenotypes, HA was 7 times more common than LA. Specimens exhibiting LA presented only with the double-positive phenotype.
HA is the predominant component of NV in corneal pathologies. LA accompanies HA; however, isolated LA (from lymphatics in the conjunctiva) does not occur in these corneal pathologies. Our results suggest the potential therapeutic utility of targeting antineovascular therapies specifically for corneal HA and/or LA pathology.
我们对 13 种潜在病理的人类角膜标本中存在的血管生成(HA)和淋巴管生成(LA)进行了特征描述。
从同意的受试者中获得人类角膜标本(每种病理 2 或 3 例标本,n=35)。用苏木精和伊红(H&E)染色确定是否存在角膜新生血管(NV)以及 NV 在浅层或深层基质中的分布。然后进行免疫组织化学染色,以区分 HA(CD31 阳性)和 LA(LYVE-1 阳性)。
21 个标本(60%)表现出双阴性(CD31(-)/LYVE-1(-))免疫染色,表明不存在 NV。12 个标本(34%)表现出 CD31(-)/LYVE-1(-),表明存在 HA 且不存在 LA。2 个标本(6%)表现出双阳性(CD31(+)/LYVE-1(+))表型,表明同时存在 HA 和 LA。值得注意的是,标本中未检测到 CD31(-)/LYVE-1(-)表型,表明存在 LA 且不存在 HA。深层基质 NV 与浅层基质 NV 的比例为 4:3。双阴性免疫染色在非炎症性病变中更为常见,特别是与联合新生血管表型(即 CD31(+)或 LYVE-1(+))相比。在新生血管表型中,HA 比 LA 常见 7 倍。表现出 LA 的标本仅呈现双阳性表型。
HA 是角膜病变中 NV 的主要成分。LA 伴随 HA,但在这些角膜病变中不会出现来自结膜淋巴管的孤立性 LA。我们的研究结果表明,针对角膜 HA 和/或 LA 病变的靶向抗血管生成治疗具有潜在的治疗应用价值。