The role of ABCB5-expressing limbal epithelial stem cells in corneal lymphangiogenic privilege and pterygium pathogenesis

表达ABCB5的角膜缘上皮干细胞在角膜淋巴管生成特权和翼状胬肉发病机制中的作用

• 批准号: 405319121
• 负责人: Dr. Maria Notara, Ph.D.
• 金额: --
• 依托单位: Zentrum für Augenheilkunde
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405319121?language=en
• 关键词: role; ABCB5; expressing; limbal; epithelial

Limbal epithelial stem cells (LESC) are localized at the junction between the avascular cornea and the heavily (lymph)vascularized conjunctiva. LESC maintain the integrity of the corneal epithelium and express ABCB5, which is a limbal stem cell gene required for corneal development and repair. Although it has been proven both clinically and experimentally that LESC destruction compromises corneal avascularity, the exact mechanisms behind this remain unclear.Exposure to UV irradiation is one mechanism known to compromise the LESC niche and is associated with pterygium, a non-cancerous tumour of the conjunctiva which grows onto the cornea and compromises corneal avascularity and vision. Our own preliminary data suggest that limbal epithelial stem cells become differentiated under UV exposure, thus leading to a pro-inflammatory and prolymphangiogenic micromillieu in the limbal stem cell niche. Furthermore, our own early data show damage to ABCB5+ LESC in human pterygium tissue. Our overall hypothesis is that while under normal circumstances, LESCs expressing ABCB5 contribute to corneal avascularity, following UV-induced damage they contribute to neovascularization and induction of pterygia.Therefore, we aim to: 1. better understand the molecular mechanisms by which ABCB5-positive LESCs contribute to corneal avascularity and thereby identify novel regulators of corneal lymphangiogenic privilege and 2. unravel if and how UV light, known to be associated with pterygium pathogenesis, damages ABCB5-positive LESCs. Overall, a better understanding of the putative anti(lymph)angiogenic mechanisms exerted by ABCB5-positive limbal epithelial stem cells and their potential damage by UV light will eventually help to develop new treatment options against neovascular corneal and ocular surface diseases.

角膜缘上皮干细胞（LESC）定位于无血管角膜和大量（淋巴）血管化结膜之间的连接处。LESC维持角膜上皮的完整性，并表达ABCB5， ABCB5是角膜发育和修复所需的角膜缘干细胞基因。尽管临床和实验都证明LESC破坏会损害角膜血管，但其背后的确切机制尚不清楚。暴露于紫外线照射是一种已知的损害LESC生态位的机制，并与翼状胬肉有关，翼状胬肉是一种结膜的非癌性肿瘤，生长在角膜上，损害角膜血管和视力。我们自己的初步数据表明，角膜缘上皮干细胞在紫外线照射下分化，从而导致角膜缘干细胞生态位中的促炎和促淋巴管生成微微细胞。此外，我们自己的早期数据显示ABCB5+ LESC在人翼状组织中受损。我们的总体假设是，虽然在正常情况下，表达ABCB5的LESCs有助于角膜无血管，但在紫外线诱导损伤后，它们有助于新生血管和诱导翼状胬肉。因此，我们的目标是：1。更好地理解abcb5阳性的LESCs促进角膜血管缺乏的分子机制，从而确定角膜淋巴管生成特权的新调节因子。揭示与翼状胬肉发病机制相关的紫外线是否以及如何损害abcb5阳性的LESCs。总之，更好地了解abcb5阳性角膜缘上皮干细胞可能发挥的抗（淋巴）血管生成机制及其在紫外线下的潜在损伤，将最终有助于开发针对新生血管性角膜和眼表疾病的新治疗方案。