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 journalArticle

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

Fingerprint

Inositol 1,4,5-Trisphosphate Receptors
Tears
Water supply
Infiltration
Autoantibodies
Epinephrine
Acetylcholine
eyes
secretion
receptors
mice
lacrimal apparatus
Lacrimal Apparatus
acinar cells
Acinar Cells
calcium
autoantibodies
Water Supply
acetylcholine
epinephrine

ASJC Scopus subject areas

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

Cite this

Inaba, T., Hisatsune, C., Sasaki, Y., Ogawa, Y., Ebisui, E., Ogawa, N., ... 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

Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye. / Inaba, Takaaki; Hisatsune, Chihiro; Sasaki, Yasumasa; Ogawa, Yoko; Ebisui, Etsuko; Ogawa, Naoko; Matsui, Minoru; Takeuchi, Tsutomu; Mikoshiba, Katsuhiko; Tsubota, Kazuo.

In: PLoS One, Vol. 9, No. 6, e99205, 05.06.2014.

Research output: Contribution to journalArticle

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, vol. 9, no. 6, e99205. https://doi.org/10.1371/journal.pone.0099205
Inaba T, Hisatsune C, Sasaki Y, Ogawa Y, Ebisui E, Ogawa N et al. Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye. PLoS One. 2014 Jun 5;9(6). e99205. https://doi.org/10.1371/journal.pone.0099205
Inaba, Takaaki ; Hisatsune, Chihiro ; Sasaki, Yasumasa ; Ogawa, Yoko ; Ebisui, Etsuko ; Ogawa, Naoko ; Matsui, Minoru ; Takeuchi, Tsutomu ; Mikoshiba, Katsuhiko ; Tsubota, Kazuo. / Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye. In: PLoS One. 2014 ; Vol. 9, No. 6.
@article{018aec7c47894b64af4ef2e8e1e7ef07,
title = "Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye",
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 Sj{\"o}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.",
author = "Takaaki Inaba and Chihiro Hisatsune and Yasumasa Sasaki and Yoko Ogawa and Etsuko Ebisui and Naoko Ogawa and Minoru Matsui and Tsutomu Takeuchi and Katsuhiko Mikoshiba and Kazuo Tsubota",
year = "2014",
month = "6",
day = "5",
doi = "10.1371/journal.pone.0099205",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye

AU - Inaba, Takaaki

AU - Hisatsune, Chihiro

AU - Sasaki, Yasumasa

AU - Ogawa, Yoko

AU - Ebisui, Etsuko

AU - Ogawa, Naoko

AU - Matsui, Minoru

AU - Takeuchi, Tsutomu

AU - Mikoshiba, Katsuhiko

AU - Tsubota, Kazuo

PY - 2014/6/5

Y1 - 2014/6/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84902531838&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902531838&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0099205

DO - 10.1371/journal.pone.0099205

M3 - Article

C2 - 24901844

AN - SCOPUS:84902531838

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e99205

ER -