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, particularly, in 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. Herein, an asymmetrical distribution of mast cells was shown at the murine ocular surface, with the higher number of mast cells distributed along the nasal limbus of the cornea compared with the temporal side. Using a well-characterized murine model of suture-induced corneal neovascularization, insult to the nasal side was shown to result in more extensive angiogenesis compared with 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 (cKit^w-sh). Unlike the wild-type (C57BL/6) mice, cKit^w-sh mice did not show disproportionate growth of corneal blood vessels following the temporal and nasal insult. Moreover, cromolyn-mediated pharmacologic blockade of mast cells at the ocular surface attenuated the asymmetrical nasal and temporal neovascularization, suggesting that spatial distribution of mast cells significantly contributes to angiogenic response at the ocular surface.