Monocyte-derived Wnt Signal Regulates Corneal Inflammatory Lymphangiogenesis

Abstract

Purpose: The Wnt system is known to be involved in multiple functions, such as cell fate determination and stem cell maintenance. However, to date, there is little information about its roles in lymphangiogenesis, a pathological process associated with many diseases. In this study, we investigated the effect of monocyte-derived Wnt signaling in inflammatory lymphangiogenesis in the cornea.

Methods: Wntless (Wls) gene, which binds to Wnt proteins and facilitates Wnt sorting and secretion, was targeted for conditional deletion in murine monocytes. The transgenic mice were generated by cross breeding of Csf1R-cre and Wls-flox animals. Standard suture placement model was used to induce corneal inflammatory lymphangiogenesis in heterozygous mice or littermate controls. Whole-mount corneas were harvested for anti-LYVE-1 staining. Digital images from immunofluorescent microscopic assays were analyzed by NIH Image J software.

Results: Corneal lymphangiogenic response in heterozygous mice carrying monocytic specific Wls deletion was significantly suppressed compared to control littermates, as assessed by lymphatic invasion area.

Conclusions: This study shows that monocyte-derived Wnt signaling is critically involved in lymphatic vessel formation during inflammation. Further investigation on this observation may lead to the development of new cellular or molecular targeting strategies for lymphatic diseases occurring both inside and outside the eye.