%0 Journal Article
%T Mice Lacking Inositol 1,4,5-Trisphosphate Receptors Exhibit Dry Eye
%A Takaaki Inaba
%A Chihiro Hisatsune
%A Yasumasa Sasaki
%A Yoko Ogawa
%A Etsuko Ebisui
%A Naoko Ogawa
%A Minoru Matsui
%A Tsutomu Takeuchi
%A Katsuhiko Mikoshiba
%A Kazuo Tsubota
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0099205
%X Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3 (Itpr2£¿/£¿;Itpr3£¿/£¿double-knockout mice). We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2£¿/£¿;Itpr3£¿/£¿ mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2£¿/£¿;Itpr3£¿/£¿ mice. Consequently, Itpr2£¿/£¿;Itpr3£¿/£¿ mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sj£¿gren¡¯s syndrome (SS) in humans, were also detected in older Itpr2£¿/£¿;Itpr3£¿/£¿ mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2£¿/£¿;Itpr3£¿/£¿ mice could be a new dry eye mouse model with symptoms that mimic those of SS.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0099205