Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye

Takaaki Inaba, Chihiro Hisatsune, Yasumasa Sasaki, Yoko Ogawa, Etsuko Ebisui, Naoko Ogawa, Minoru Matsui, Tsutomu Takeuchi, Katsuhiko Mikoshiba, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

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 Ca 2+ 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 Sjögren'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.

Original languageEnglish
Article numbere99205
JournalPloS one
Volume9
Issue number6
DOIs
Publication statusPublished - 2014 Jun 5

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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