The lymphatic vasculature is - amongst other tasks - essentially involved in
inflammation, (auto)immunity, graft rejection and
cancer metastasis. The eye is mainly devoid of lymphatic vessels except for its adnexa, the conjunctiva and the limbus. However, several pathologic conditions can result in the secondary ingrowth of lymphatic vessels into physiologically alymphatic parts of the eye such as the cornea or the inner eye. Therefore, the cornea has served as an excellent in vivo model system to study lymphangiogenesis, and findings from such studies have substantially contributed to the understanding of central principles of lymphangiogenesis also with relevance outside the eye. Grafting experiments at the cornea have been extensively used to analyze the role of lymphangiogenesis in transplant immunology. In this regard, we recently demonstrated the crucial role of lymphatic vessels in mediating corneal allograft rejection and could show that antilymphangiogenic
therapy increases graft survival. In the field of
cancer research, we recently detected
tumor-associated lymphangiogenesis in the most common malignant
tumors of the eye, such as conjunctival
carcinoma and
melanoma, and ciliochoroidal
melanoma with extraocular extension. These neolymphatics correlate with an increased risk of local recurrence,
metastasis and
tumor related death, and may offer potential therapeutic targets for the treatment of these
tumors. This review will focus on corneal and
tumor-associated ocular lymphangiogenesis. First, we will describe common experimentally used corneal lymphangiogenesis models and will recapitulate recent findings regarding the involvement of lymphatic vessels in
corneal diseases and transplant immunology. The second part of this article will summarize findings about the participation of
tumor-associated lymphangiogenesis in ocular
malignancies and their implications for the development of future therapeutic strategies.