Novel Characterization of Lymphatic Valve Formation during Corneal Inflammation

Lymphatic research has progressed rapidly in recent years. Though lymphatic dysfunction has been found in a wide array of disorders from transplant rejection to cancer metastasis, to date, there is still little effective treatment for lymphatic diseases. The cornea offers an optimal site for lymphatic research due to its accessible location, transparent nature, and lymphatic-free but inducible features. However, it still remains unknown whether lymphatic valves exist in newly formed lymphatic vessels in the cornea, and how this relates to an inflammatory response. In this study, we provide the first evidence showing that lymphatic valves were formed in mouse cornea during suture-induced inflammation with the up-regulation of integrin alpha 9. The number of corneal valves increased with the progression of inflammatory lymphangiogenesis. Moreover, we have detected lymphatic valves at various developmental stages, from incomplete to more developed ones. In addition to defining the average diameter of lymphatic vessels equipped with lymphatic valves, we also report that lymphatic valves were more often located near the branching points. Taken together, these novel findings not only provide new insights into corneal lymphatic formation and maturation, but also identify a new model for future investigation on lymphatic valve formation and possibly therapeutic intervention

Effects of substance P on mesenteric lymphatic contractility in the rat

Substance P (SP) is associated with lymphatic tissue and is a putative mediator of inflammation. The lymph pump is one of the major "safety factors" preventing edema and its activity is altered by inflammatory mediators. The impact of SP on lymphatics was studied in the rat mesentery. METHODS AND RESULTS: Rats were prepared for in situ lymphatic observation using intravital videomicroscopic techniques. Sections of the small intestine and mesentery were exteriorized and superfused. Lymphatic diameters were measured and pumping activity was determined from the lymphatic diameter tracing. Lymph pump parameters evaluated included diastolic diameter, systolic diameter, contraction frequency, stroke volume, and lymph pump flow. After a control period, the tissues were exposed to SP (10(-9), 10(-8), 10(-7), 10(-6) M). SP reduced both diameters and increased contraction frequency in a concentration-dependent manner. SP (1.0 microM) produced the following changes (% of control): reductions in diastolic diameter (50%), systolic diameter (55%), and stroke volume (63%); a large increase in contraction frequency (661%); and a modest increase in lymph pump flow (44%). SP also stimulated vessels that were not contracting phasically to develop typical contraction patterns. CONCLUSIONS: Although SP produced a tonic constriction of the lymphatics, lymph pump flow was maintained or slightly elevated via an increase in contraction frequency. SP also induced pumping activity in lymphatics that were previously quiescent, thereby further stimulating flow. These effects may serve to minimize the formation of edema in face of the inflammatory edemagenic conditions produced by SP