Clahsen Thomas, Büttner Christian, Hatami Niloofar, Reis André, Cursiefen Claus
Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany.
Center for Molecular Medicine (CMMC), University of Cologne, 50937 Cologne, Germany.
J Clin Med. 2020 Feb 9;9(2):479. doi: 10.3390/jcm9020479.
Under normal conditions, the cornea, being the transparent "windscreen" of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem- and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem- and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea.
在正常情况下，角膜作为眼睛的透明“挡风玻璃”，没有血管和淋巴管。然而，眼部的各种疾病，如感染，会干扰促进和抑制因子之间的平衡，从而导致血管和淋巴管向内生长。新形成的淋巴管会增加后续角膜移植后移植物排斥的风险。角膜移植是全球最常见的移植手术之一，欧洲每年有超过4万例手术。迄今为止，已经专门针对角膜血管内皮生长因子（VEGF）途径开发了各种抗血管生成和抗淋巴管生成的治疗策略。然而，目前尚无临床可用的特异性调节淋巴管生成的治疗策略。在本综述中，我们将概述血管生成和淋巴管生成的内源性调节因子，并讨论靶向病理性淋巴管生成的潜在新策略。此外，我们将回顾最近发现的调节剂，并证明角膜是鉴定新型淋巴管生成内源性调节剂的合适模型。鉴定新型淋巴管生成调节剂并更好地理解相关信号通路将有助于开发治疗病理性淋巴管生成的新治疗靶点。这反过来将改善移植物排斥反应，不仅对角膜移植有效。
