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Francine F Behar-Cohen, elodie bousquet, Min Zhao, Brigitte Goldenberg, Lorena Vieira, Marie-Christine Naud, Ciara Bergin, Yvonne De Kozak; Choroidal mast cells in retinal pathology: a potential target for intervention. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4720.
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We previously showed that mast cells play a role in the initiation of acute ocular inflammation but the exact consequences of mast cell degranulation on ocular pathology have not been fully characterized. The aim of this study was to analyse in depth the kinetics of events following local and acute ocular mast cells degranulation.
Adult female Lewis rats (6-8 weeks old, Janvier, Le Genest-Saint-Isle, France) were used in this study. Animals were housed in a 12-hrs light and 12-hrs dark cycle and fed water and dried ration ad libitum. Experimental procedures were submitted and approved by the ethic committee of Paris Descartes University (number: Ce5/2012/122).<br /> We induced mast cells depletion of their inflammatory mediators by the local unilateral sub-conjunctival injection of 48/80 drug. Clinical examination (slit-lamp, SD-OCT) were preformed and animals were sacrificed at different time points for pathology and cytokines analysis.
Initial degranulation of mast cells was observed in the choroid 15 min after the injection of 48/80, with degranulation continuing to increase up to 3-6 hrs after the injection. The signs of anterior segment clinical inflammation paralleled mast cell degranulation. Posterior segment imaging using optical coherence tomography showed increased choroidal thickness and serous retinal detachments, which were confirmed by histological analysis. The infiltration of polymorphonuclear cells was associated with increased ocular media levels of TNF-a at 1 and 3 hrs, followed by CXCL1, IL-6, IL-5, CCL-2 at 6 and 24 hrs, and IL-1b at 24 hrs. Analysis of levels of VEGF and IL-18 at all time intervals showed an opposite evolution of VEGF as compared to IL-18 levels.
These findings suggest that the local degranulation of ocular mast cells provokes acute ocular inflammation, increased choroidal vascular permeability and serous retinal detachments. The involvement of mast cells in retinal diseases, particularly when associated with serous detachments, should be investigated and the pharmacological inhibition of mast cells degranulation considered as a potential intervention target.
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