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Evaluation of Longitudinal Lymphatic Function Changes upon Injury in the Mouse Tail with Photodynamic Therapy

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Abstract

Purpose

The lymphatic system is an essential but often understudied component of the circulatory system in comparison with its cardiovascular counterpart. Such disparity could often be explained by the difficulty in imaging lymphatics and the specialized microsurgical skills that are often required for lymphatic injury models. Recently, it has been shown that verteporfin, a photosensitive drug used for photodynamic therapy (PDT) to ablate the blood vessels, provides a similar effect on lymphatic vessels. Here, we seek to administer verteporfin and perform a modified form of PDT on collecting lymphatics in the mouse tail, a commonly used location for the study of lymphatic disorders, and examine lymphatic remodeling, contractility, and transport in response to the procedure.

Methods

Mice collecting lymphatics in the tail were injured by PDT through an intradermal injection of verteporfin in the distal tip of the tail followed by light activation on the proximal portion of the tail downstream of the injection site. Lymphatic function was evaluated using a near-infrared (NIR) imaging system weekly for up to 28 days after injury.

Results

PDT resulted in a loss in lymphatic function contractile frequency that persisted for up to 7 days after injury. Packet transport and packet amplitude, measurements reflective of the strength of contraction, were significantly reduced 14 days after injury. The lymphatics showed a delayed increase in lymphatic leakage at 7 days that persisted until the study endpoint on day 28.

Conclusion

This technique provides an easy-to-use method for injuring lymphatics to understand their remodeling response to injury by PDT as well as potentially for screening therapeutics that seek to normalize lymphatic permeability or contractile function after injury.

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Acknowledgments

This work was funded by The National Institutes of Health (Grant No. R01-HL113061) and Naumann-Etienne Foundation (Kuzminich).

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical Approval

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate Institutional Committees.

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Authors and Affiliations

  1. Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA

    Yanina Kuzminich & J. Brandon Dixon

  2. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Yanina Kuzminich & J. Brandon Dixon

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  1. Yanina Kuzminich
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Correspondence to J. Brandon Dixon.

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Kuzminich, Y., Dixon, J.B. Evaluation of Longitudinal Lymphatic Function Changes upon Injury in the Mouse Tail with Photodynamic Therapy. Cardiovasc Eng Tech 14, 204–216 (2023). https://doi.org/10.1007/s13239-022-00645-z

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