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Rose Mathew, Nancy Reyes, Tomas Blanco, Daniel R Saban; Corneal Lymphangiogenesis Contributes to Egress of Corneal Dendritic Cells in a Mouse Model of Ocular Allergy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1858.
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Our group has previously shown for the first time that neolymphatic vessels invade the cornea in a mouse model of ocular allergy. However, the function of such corneal lymphangiogenic processes in antigen transport to the lymph node has yet to be determined. We herein examined the potential for egress of antigen-laden dendritic cells (DCs) from the cornea via such corneal lymphatic vessels.
C57BL/6 mice (CD45.2) were immunized with ovalbumin, pertussis toxin and aluminum hydroxide and subsequently challenged topically with allergen to trigger corneal lymphangiogenesis in ocular allegy. Such allergy induced mice were injected intrastromally with 5x104 OVA-pulsed C57BL/6 bone marrow derived DCs (CD45.1). Mice were simultaneously treated topically with or without the addition of topical CCR7 blocking antibody—which inhibits egress of DCs through terminal lymphatic vessels. A cohort of naïve mice injected with DCs was also included as an additional control. Corneas were harvested 6h and 24h post-injection and examined for DC distribution by CD45.1 and the presence of lymphatic vessels was assessed by LYVE-1 staining. Micrographs were analyzed using Imaris software.
Injected DCs being CD45.1 could be easily distinguished from the host CD45.2 cells by whole-mount confocal microscopy. In naïve control mice, such DCs were found randomly scattered throughout the peripheral cornea. This was in marked contrast with corneas of allergy-induced mice, wherein injected DCs were seen heavily concentrated around lymphatic sprouts adjacent to the limbus, as well as around lymphatic vessels in limbal arcade. Interestingly, CCR7 blockade in allergy induced mice exhibited strikingly high numbers of injected DCs that remained and were interspersed throughout the width of the entire cornea, including the central region.
The marked concentration of injected DCs found along corneal lymphatic vessels in allergic mice, which was not similarly seen in naïve controls, suggests a functional role for allergy-induced corneal lymphangiogenesis in the egress of allergen-laden corneal DCs. This observation is indeed supported by CCR7 blockade data, which showed strikingly high numbers and diffuse interspersion of injected DCs in the corneas of allergic mice. These data may therefore implicate a role for corneal DCs in the activation of T cell responses in ocular allergy.
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