Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermisReport as inadecuate




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Angiogenesis

, Volume 17, Issue 2, pp 347–357

First Online: 28 July 2013Received: 10 January 2013Accepted: 24 June 2013DOI: 10.1007-s10456-013-9365-6

Cite this article as: Kilarski, W.W., Muchowicz, A., Wachowska, M. et al. Angiogenesis 2014 17: 347. doi:10.1007-s10456-013-9365-6

Abstract

Lymphatic vessels transport fluid, antigens, and immune cells to the lymph nodes to orchestrate adaptive immunity and maintain peripheral tolerance. Lymphangiogenesis has been associated with inflammation, cancer metastasis, autoimmunity, tolerance and transplant rejection, and thus, targeted lymphatic ablation is a potential therapeutic strategy for treating or preventing such events. Here we define conditions that lead to specific and local closure of the lymphatic vasculature using photodynamic therapy PDT. Lymphatic-specific PDT was performed by irradiation of the photosensitizer verteporfin that effectively accumulates within collecting lymphatic vessels after local intradermal injection. We found that anti-lymphatic PDT induced necrosis of endothelial cells and pericytes, which preceded the functional occlusion of lymphatic collectors. This was specific to lymphatic vessels at low verteporfin dose, while higher doses also affected local blood vessels. In contrast, light dose fluence did not affect blood vessel perfusion, but did affect regeneration time of occluded lymphatic vessels. Lymphatic vessels eventually regenerated by recanalization of blocked collectors, with a characteristic hyperplasia of peri-lymphatic smooth muscle cells. The restoration of lymphatic function occurred with minimal remodeling of non-lymphatic tissue. Thus, anti-lymphatic PDT allows control of lymphatic ablation and regeneration by alteration of light fluence and photosensitizer dose.

KeywordsEndothelium Lymphatic collectors Intravital imaging Lymphangiogenesis Lymphangiography Lymphatic ablation Reactive oxygen species Verteporfin Visudyne PDT AbbreviationsBMBasement membrane

PDTPhotodynamic therapy

PIPropidium iodide

SMCSmooth muscle cell

TRITC-dextranTetramethyl rhodamine iso-thiocyanate-dextran

Angelika Muchowicz and Malgorzata Wachowska contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s10456-013-9365-6 contains supplementary material, which is available to authorized users.

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Author: Witold W. Kilarski - Angelika Muchowicz - Malgorzata Wachowska - Renata Mężyk-Kopeć - Jakub Golab - Melody A. Swartz -

Source: https://link.springer.com/







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