Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Urology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Cells. 2023 Jan 14;12(2):319. doi: 10.3390/cells12020319.
Corneal lymphangiogenesis is one component of the neovascularization observed in several inflammatory pathologies of the cornea including dry eye disease and corneal graft rejection. Following injury, corneal (lymph)angiogenic privilege is impaired, allowing ingrowth of blood and lymphatic vessels into the previously avascular cornea. While the mechanisms underlying pathological corneal hemangiogenesis have been well described, knowledge of the lymphangiogenesis guidance mechanisms in the cornea is relatively scarce. Various signaling pathways are involved in lymphangiogenesis guidance in general, each influencing one or multiple stages of lymphatic vessel development. Most endogenous factors that guide corneal lymphatic vessel growth or regression act via the vascular endothelial growth factor C signaling pathway, a central regulator of lymphangiogenesis. Several exogenous factors have recently been repurposed and shown to regulate corneal lymphangiogenesis, uncovering unique signaling pathways not previously known to influence lymphatic vessel guidance. A strong understanding of the relevant lymphangiogenesis guidance mechanisms can facilitate the development of targeted anti-lymphangiogenic therapeutics for corneal pathologies. In this review, we examine the current knowledge of lymphatic guidance cues, their regulation of inflammatory states in the cornea, and recently discovered anti-lymphangiogenic therapeutic modalities.
角膜淋巴管生成是几种角膜炎症性疾病(包括干眼症和角膜移植排斥反应)中观察到的新生血管形成的一个组成部分。在损伤后,角膜(淋)血管生成特权受到损害,允许血液和淋巴管侵入先前无血管的角膜。虽然病理性角膜血管生成的机制已经得到很好的描述,但对角膜淋巴管生成的指导机制的了解相对较少。一般来说,各种信号通路参与淋巴管生成的指导,每个通路都影响淋巴管发育的一个或多个阶段。大多数指导角膜淋巴管生长或消退的内源性因素都通过血管内皮生长因子 C 信号通路起作用,该通路是淋巴管生成的中央调节剂。最近,一些外源性因素被重新利用并显示出可调节角膜淋巴管生成,揭示了以前未知的影响淋巴管导向的独特信号通路。深入了解相关的淋巴管生成指导机制有助于为角膜疾病开发靶向抗淋巴管生成治疗方法。在这篇综述中,我们检查了淋巴管生成指导线索的最新知识,它们对角膜炎症状态的调节,以及最近发现的抗淋巴管生成治疗方法。