Yuen Don, Leu Rose, Sadovnikova Anna, Chen Lu
Center for Eye Disease and Development, Program in Vision Science, School of Optometry, University of California , Berkeley, USA.
Lymphat Res Biol. 2011;9(2):109-14. doi: 10.1089/lrb.2011.0005.
Corneal lymphangiogenesis (LG) and hemangiogenesis (HG) accompany many diseases after inflammatory, infectious, traumatic or chemical insults. They also contribute to transplant rejection. It is known that corneal transplants in infants or children have a higher rejection rate than in adults. However, it has never been studied whether infant corneas differ from adult corneas in inflammatory LG, HG, or both, which is the focus of this study.
Corneal inflammatory LG and HG were induced by a standard suture placement model in C57BL/6 mice of 3 weeks and 8 weeks of age, respectively. Corneal LG, HG, and macrophage infiltration were assessed by immunofluorescent microscopic studies using specific antibodies against CD31 (a panendothelial cell marker), LYVE-1 (a lymphatic marker), and F4/80 (a macrophage marker). Blood vessels were also examined by ophthalmic slit-lamp microscopic assays in vivo. Digital images were analyzed by NIH Image J software. It was found, for the first time, that infant corneas exhibited a higher level of LG, HG, and macrophage infiltration during inflammation. Infant lymphatic and blood vessels demonstrated greater density and invasion area but similar branching points. Additionally, infant lymphatic vessels were also of larger diameter.
Infant and adult corneas differ greatly in their inflammatory responses of LG, HG, and macrophage infiltration. These novel findings will shed some light on our understanding of the LG and HG processes, as well as the development of new therapeutic protocols for corneal diseases, particularly, in infants or children, where an early restoration of sight is critically important in preventing amblyopia or permanent vision loss.
角膜淋巴管生成(LG)和血管生成(HG)伴随许多炎症、感染、创伤或化学损伤后的疾病。它们也促成移植排斥反应。已知婴儿或儿童的角膜移植排斥率高于成人。然而,婴儿角膜在炎症性LG、HG或两者方面是否与成人角膜不同从未被研究过,这是本研究的重点。
分别在3周龄和8周龄的C57BL/6小鼠中通过标准缝线植入模型诱导角膜炎症性LG和HG。使用针对CD31(一种泛内皮细胞标志物)、LYVE-1(一种淋巴管标志物)和F4/80(一种巨噬细胞标志物)的特异性抗体,通过免疫荧光显微镜研究评估角膜LG、HG和巨噬细胞浸润。还通过体内眼科裂隙灯显微镜检查法检查血管。数字图像由NIH Image J软件分析。首次发现,婴儿角膜在炎症期间表现出更高水平的LG、HG和巨噬细胞浸润。婴儿的淋巴管和血管显示出更大的密度和侵袭面积,但分支点相似。此外,婴儿淋巴管的直径也更大。
婴儿和成人角膜在LG、HG和巨噬细胞浸润的炎症反应方面有很大差异。这些新发现将有助于我们理解LG和HG过程,以及开发针对角膜疾病的新治疗方案,特别是在婴儿或儿童中,早期恢复视力对于预防弱视或永久性视力丧失至关重要。