角膜淋巴管生成在干眼中的研究进展

Advances in Corneal Lymphangiogenesis in Dry Eyes

摘要: 干眼(Dry Eye Disease, DED)是一种常见的多因素眼表疾病，其核心机制涉及泪膜不稳定、眼表炎症和高渗透压。近年来，研究揭示角膜淋巴管生成(Corneal Lymphangiogenesis)在DED中发挥关键作用，促进免疫细胞迁移和炎症放大，角膜淋巴管生成由多种内外部因素引发，被视为慢性炎症性疾病，涉及适应性免疫和固有免疫的激活，进而导致角膜上皮和泪腺功能障碍，形成恶性循环。正常情况下，角膜无血管且具备血管生成和淋巴管生成的免疫赦免特性，但在干眼模型中，已发现区域淋巴结中角膜抗原呈递细胞被激活，提示可能有新的角膜淋巴管形成。随着可靠的淋巴管细胞表面标志物(如LYVE-1、CCL21、FOXC2、VEGFR-3等)的出现，角膜淋巴管生成的研究得以深入开展。众多研究表明，角膜淋巴管生成在干眼发病机制中起着重要作用，这使得抗淋巴管生成治疗策略有望成为治疗干眼的可行方案，且已有少量临床试验对干眼的抗淋巴管生成方式进行了验证。

Abstract: Dry Eye Disease (DED) is a common multifactorial ocular surface disorder, whose core mechanisms involve tear film instability, ocular surface inflammation, and hyperosmolarity. In recent years, studies have revealed that corneal lymphangiogenesis plays a crucial role in DED, promoting immune cell migration and inflammation amplification. Corneal lymphangiogenesis is triggered by a variety of internal and external factors and is regarded as a chronic inflammatory condition. It involves the activation of both adaptive and innate immunity, which in turn leads to corneal epithelial and lacrimal gland dysfunction, forming a vicious cycle. Under normal circumstances, the cornea is avascular and possesses the immune privilege characteristic of resisting angiogenesis and lymphangiogenesis. However, in dry eye models, the activation of corneal antigen-presenting cells in regional lymph nodes has been observed, suggesting the potential formation of new corneal lymphatic vessels. With the identification of reliable lymphatic vessel cell surface markers (such as LYVE-1, CCL21, FOXC2, VEGFR-3, etc.), in-depth research on corneal lymphangiogenesis has been enabled. Numerous studies have demonstrated that corneal lymphangiogenesis plays a significant role in the pathogenesis of dry eye disease, making anti-lymphangiogenic therapeutic strategies a promising viable option for DED treatment. Additionally, a small number of clinical trials have been conducted to validate anti-lymphangiogenic approaches for dry eye disease.