Identification of novel endogenous modulators of (inflammatory) lymphangiogenesis by analyzing mouse strain-specific differences

角膜是分析血管和淋巴管生长(血管生成和淋巴管生成)机制的成熟模型。角膜作为模型的优势在于它的生理无血管和透明性。尽管如此，与患者一样，在实验中发生炎症后，角膜缘原有血管产生的血管和淋巴管都可以生长到角膜中。在患者中，这不仅会降低视力，还会增加随后的角膜移植后免疫反应的风险。我们小组以前的数据表明，在炎症条件下和健康静息角膜的角膜缘中，角膜淋巴管的生成随应变的不同而不同。然而，个体间差异的潜在遗传原因尚未得到详细研究。因此，该项目的重点在于识别导致观察到的菌株依赖差异的候选基因，并分析新的淋巴管调节候选基因的分子通路。靶向新型内源性调节因子不仅可以减少角膜移植后的免疫反应，提高移植物的存活率，而且可以用于治疗淋巴源性转移的肿瘤和调节炎症过程。

The cornea is a well established model to analyze the mechanisms of blood and lymphatic vessel growth (angiogenesis and lymphangiogenesis). Advantages of the cornea as a model are its physiological avascularity and transparency. Nonetheless, following inflammation experimentally as in patients, both blood and lymphatic vessels arising from pre-existing vessels in the corneal limbus can grow into the cornea. In patients this not only reduces vision but also increases the risk for immune reactions after subsequent corneal transplantation. Previous data from our group demonstrate that corneal lymphangiogenesis differs strain-dependently between mouse strains under inflammatory conditions and additionally in the limus of the healthy resting cornea. However, the underlying genetic causes of the inter-individual differences have not been studied in detail yet. Therefore, the focus of the project lies on the identification of candidate genes which are responsible for the observed strain dependent differences and on the analysis of molecular pathways of novel lymphangioregulatory candidates. Targeting of novel endogenous regulators could not only reduce immune reactions and promote graft survival after (corneal) transplantation but also could be used to treat tumors with lymphogenic metastasis and regulate inflammatory processes.