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

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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

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ASJC Scopus subject areas

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

Cite this

Inaba, T., Hisatsune, C., Sasaki, Y., Ogawa, Y., Ebisui, E., Ogawa, N., Matsui, M., Takeuchi, T., Mikoshiba, K., & Tsubota, K. (2014). Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye. PloS one, 9(6), [e99205]. https://doi.org/10.1371/journal.pone.0099205