Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.
Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.
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DOI：
10.1371/journal.pone.0099205
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tsubota K
中科院分区：
文献类型：
--
作者：
Inaba T;Hisatsune C;Sasaki Y;Ogawa Y;Ebisui E;Ogawa N;Matsui M;Takeuchi T;Mikoshiba K;Tsubota K
泪液分泌物是重要的，因为它为眼表提供水分并保持眼睛湿润。副交感神经和交感神经通路都有助于泪液分泌。虽然泪腺腺泡细胞内Ca 2+升高是两种途径中泪液分泌的关键事件，但负责交感神经途径中Ca 2+升高的Ca 2+通道尚未得到充分分析。在这项研究中，我们检查了缺乏肌醇1，4，5-三磷酸受体（IP 3R）2型和3型的小鼠（Itpr 2 −/−; Itpr 3 −/−双敲除小鼠）的泪液分泌。我们发现，Itpr 2 −/−; Itpr 3 −/−小鼠的副交感神经和交感神经通路的泪液分泌都被消除。在Itpr 2 −/−; Itpr 3 −/−小鼠中，乙酰胆碱和肾上腺素刺激后泪腺泡细胞内Ca 2+升高被消除。因此，Itpr 2 −/−; Itpr 3 −/−小鼠表现出角膜结膜改变和角膜上皮屏障破坏。在老年Itpr 2 −/−; Itpr 3 −/−小鼠中也检测到炎性细胞浸润到泪腺和血清自身抗体升高，这是人类干燥综合征（SS）的代表性标志物。这些结果表明，IP 3R对副交感神经和交感神经通路中的泪液分泌至关重要，Itpr 2 −/−; Itpr 3 −/−小鼠可能是一种新的干眼症小鼠模型，其症状类似于SS。
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.
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影响因子：
17.8
作者：
Dartt, Darlene A.
通讯作者：
Dartt, Darlene A.
影响因子：
4.8
作者：
Hattori, M;Suzuki, AZ;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
3.4
作者：
Fukuda, Nanaho;Shirasu, Mika;Mikoshiba, Katsuhiko
通讯作者：
Mikoshiba, Katsuhiko
影响因子：
3.4
作者：
DARTT, DA;ROSE, PE;HODGES, RR
通讯作者：
HODGES, RR
影响因子：
--
作者：
HODGES, RR;DICKER, DM;DARTT, DA
通讯作者：
DARTT, DA