Department of Ophthalmology, University of Cologne, Cologne, Germany.
Prog Retin Eye Res. 2013 May;34:89-124. doi: 10.1016/j.preteyeres.2013.01.001. Epub 2013 Jan 22.
The cornea is one of the few tissues which actively maintain an avascular state, i.e. the absence of blood and lymphatic vessels (corneal [lymph]angiogenic privilege). Nonetheless do several diseases interfere with this privilege and cause pathologic corneal hem- and lymphangiogenesis. The ingrowths of pathologic blood and lymphatic vessels into the cornea not only reduce transparency and thereby visual acuity up to blindness, but also significantly increases the rate of graft rejections after subsequent corneal transplantation. Therefore great interest exists in new strategies to target pathologic corneal (lymph)angiogenesis to promote graft survival. This review gives an overview on the vascular anatomy of the normal ocular surface, on the molecular mechanisms contributing to the corneal (lymph)angiogenic privilege and on the cellular and molecular mechanisms occurring during pathological neovascularization of the cornea. In addition we summarize the current preclinical and clinical evidence for three novel treatment strategies against ocular surface diseases based on targeting pathologic (lymph)angiogenesis: (a) modulation of the immune responses after (corneal) transplantation by targeting pathologic (lymph)angiogenesis prior to and after transplantation, (b) novel concepts against metastasis and recurrence of ocular surface tumors such as malignant melanoma of the conjunctiva by anti(lymph)angiogenic therapy and (c) new ideas on how to target ocular surface inflammatory diseases such as dry eye by targeting conjunctival and corneal lymphatic vessels. Based on compelling preclinical evidence and early data from clinical trials the novel therapeutic concepts of promoting graft survival, inhibiting tumor metastasis and dampening ocular surface inflammation and dry eye disease by targeting (lymph)angiogenesis are on their way to translation into the clinic.
角膜是少数几种能够主动维持无血管状态的组织之一，即不存在血管和淋巴管（角膜[淋巴]血管生成特权）。尽管如此，有几种疾病会干扰这种特权并导致病理性角膜血管生成和淋巴管生成。病理性血管和淋巴管侵入角膜不仅会降低透明度，从而导致视力下降直至失明，而且还会显著增加随后角膜移植后的排斥反应率。因此，人们对靶向病理性角膜（淋巴）血管生成以促进移植物存活的新策略产生了浓厚的兴趣。
本文综述了正常眼表面的血管解剖结构、参与角膜（淋巴）血管生成特权的分子机制以及角膜病理性新生血管形成过程中的细胞和分子机制。此外，我们还总结了基于靶向病理性（淋巴）血管生成的三种治疗眼表面疾病的新型治疗策略的当前临床前和临床证据：（a）通过在移植前后靶向病理性（淋巴）血管生成来调节（角膜）移植后的免疫反应，（b）针对眼表面肿瘤（如结膜恶性黑色素瘤）的转移和复发的新概念通过抗（淋巴）血管生成治疗，（c）通过靶向结膜和角膜淋巴管来治疗眼表面炎症疾病（如干眼症）的新思路。
基于令人信服的临床前证据和临床试验的早期数据，通过靶向（淋巴）血管生成来促进移植物存活、抑制肿瘤转移以及抑制眼表面炎症和干眼症的新型治疗概念正在向临床转化。
