Spatial distribution of mast cells regulates asymmetrical angiogenesis at the ocular surface.

Abstract

Mast cells, historically known for their function as effector cells in the induction of allergic diseases, reside in all vascularized tissues of the body in particular proximity to blood and lymphatic vessels. Despite being neighboring sentinel cells to blood vessels, whether the spatial distribution of mast cells regulates the degree of angiogenesis remains to be investigated. Here, we showed an asymmetrical distribution of mast cells at the murine ocular surface, with the higher number of mast cells distributed along the nasal limbus of the cornea compared to the temporal side. Using a well-characterized murine model of suture-induced corneal neovascularization, we demonstrated that insult to the nasal side results in more extensive angiogenesis compared to that to the temporal side. To directly assess the impact of the spatial distribution of mast cell on angiogenesis, neovascularization was induced in mast cell-deficient mice (cKitw-sh). Unlike the wild type (C57BL/6) mice, cKitw-sh mice did not show disproportionate growth of corneal blood vessels following the temporal and nasal insult. Moreover, cromolyn-mediated pharmacological blockade of mast cells at the ocular surface attenuates the asymmetrical nasal and temporal neovascularization, suggesting a translational implication of our novel findings that spatial distribution of mast cells significantly contributes to angiogenic response at the ocular surface.