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PLoS One. 2014 Jun 5;9(6):e99205. doi: 10.1371/journal.pone.0099205. eCollection 2014.

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

Author information

1
Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo, Japan; Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama, Japan.
2
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama, Japan.
3
Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
4
Department of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan.
5
Department of Rheumatology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
6
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama, Japan; Calcium Oscillation Project, International Cooperative Research Project-Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.

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 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 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.

PMID:
24901844
PMCID:
PMC4047094
DOI:
10.1371/journal.pone.0099205
[Indexed for MEDLINE]
Free PMC Article

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