Abstract
Purpose:
To determine how recurrent corneal inflammation, a common clinical condition, regulates corneal lymphatic vessel remodeling.
Methods:
A mouse corneal model was developed in which recurrent inflammation was stimulated by suture placement following wound recovery. Immunofluorescent microscopy was used to visualize and quantify the lymphatic vessel response. VEGFR-2 and VEGFR-3 decoy receptors were used to block VEGF-A and -C pathways during initial inflammation and recurrent inflammation.
Results:
Recurrent inflammation accelerated the development a functional lymphatic vessel network. This observation revealed a novel program of lymphangiogenesis and identified a property of lymphatic vessel memory in response to recurrent inflammation. A brief episode of initial corneal inflammation and regressed lymphatic vessels were associated with the development of lymphatic vessel memory. The spatial distribution of specialized lymphatic vessel features was distinct in these vessels. Results using the VEGFR-2 and R-3 decoy receptors demonstrated that the lymphatic vessel memory response was not dependent upon the VEGF-C or VEGF-A pathways, indicating that different molecular pathways regulate inflammatory lymphangiogenesis and lymphatic vessel memory.
Conclusions:
These findings uncover a priming mechanism to facilitate a rapid lymphatic vessel memory response: a potential important component of corneal defense.
Keywords: 557 inflammation •
765 wound healing •
480 cornea: basic science