Abstract
Lymphatic is a prerequisite for the maintenance of tissue fluid balance and immunity in the body. A body of evidence also shows that lymphangiogenesis plays important roles in the pathogenesis of diseases such as tumor metastasis and inflammation. The eye was thought to lack lymphatic vessels except for the conjunctiva; however, advances in the field, including the identification of lymphatic endothelial markers (e.g., LYVE-1 or podoplanin) and lymphangiogenic factors (e.g., VEGF-C), have revealed the exsitence and possible roles of lymphatics and lymphangiogenesis in the eye. Recent studies have shown that corneal limbus, ciliary body, lacrimal gland, orbital meninges, and extraocular muscles contain lymphatic vessels and that the choroid might have a lymphatic-like system. There is no known lymphatic outflow from the eye. However, several lymphatic channels including uveolymphatic pathway might serve the ocular fluid homeostasis. Furthermore, lymphangiogenesis plays important roles in pathological conditions in the eye including corneal transplant rejection and ocular tumor progression. Yet, the role of lymphangiogenesis in most eye diseases, especially inflammatory disease or edema, remains unknown. A better understanding of lymphatic and lymphangiogenesis in the eye will open new therapeutic opportunities to prevent vision loss in ocular diseases.
Highlights
The lymphatic system in human was first described by Gasper Aselli in 1627 in a paper “De Lacteibus sive Lacteis Venis,” Quarto Vasorum Mesarai corum Genere novo invento
The lymph is transported via precollectors to collecting lymphatic vessels and is returned through the lymphaticovenous junctions between the thoracic or lymphatic duct and the subclavian veins to the blood circulation [1]
Maruyama et al showed that CD11b(+) macrophages infiltrate the inflammatory cornea and transdifferentiate into lymphatic endothelium that contributes to lymphangiogenesis [42]
Summary
The lymphatic system in human was first described by Gasper Aselli in 1627 in a paper “De Lacteibus sive Lacteis Venis,” Quarto Vasorum Mesarai corum Genere novo invento. The lymph is transported via precollectors to collecting lymphatic vessels and is returned through the lymphaticovenous junctions between the thoracic or lymphatic duct and the subclavian veins to the blood circulation [1] Another role of the lymphatics is to carry immune cells to the lymph nodes and to control the immunity in health and disease. Histological studies show the location and existence of lymphatics in the eye [7] These studies have revealed that lymphatics contribute to the ocular homeostasis and that ocular lymphangiogenesis may play important roles in eye disorders. VEGF-A has important roles in mammalian vascular development and in diseases involving abnormal growth of blood vessels. Various studies clarify the involvement of VEGF-C and -D/VEGFR-3 system in cancer lymphatic invasion and lymph node metastasis [12, 13]. VEGF-C and -D/VEGFR-3 signaling is involved in inflammatory diseases and organ transplantation [6, 14, 15]
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