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 language | English |
|---|---|
| Article number | e99205 |
| Journal | PLoS One |
| Volume | 9 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2014 Jun 5 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
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 -