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缺乏肌醇1,4,5-三磷酸受体的小鼠表现出干眼症。

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

作者信息

Inaba Takaaki, Hisatsune Chihiro, Sasaki Yasumasa, Ogawa Yoko, Ebisui Etsuko, Ogawa Naoko, Matsui Minoru, Takeuchi Tsutomu, Mikoshiba Katsuhiko, Tsubota Kazuo

机构信息

Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo, Japan; Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama, Japan.

Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama, Japan.

出版信息

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

DOI:10.1371/journal.pone.0099205
PMID:24901844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4047094/
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.

摘要

泪液分泌很重要，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参与泪液分泌。尽管泪腺腺泡细胞内的Ca2+升高是两条通路中泪液分泌的关键事件，但负责交感神经通路中Ca2+升高的Ca2+通道尚未得到充分分析。在本研究中，我们检测了缺乏2型和3型肌醇1,4,5-三磷酸受体（IP3R）的小鼠（Itpr2-/-;Itpr3-/-双敲除小鼠）的泪液分泌情况。我们发现，Itpr2-/-;Itpr3-/-小鼠的副交感神经和交感神经通路中的泪液分泌均被消除。Itpr2-/-;Itpr3-/-小鼠在乙酰胆碱和肾上腺素刺激后泪腺腺泡细胞内的Ca2+升高被消除。因此，Itpr2-/-;Itpr3-/-小鼠出现了角结膜改变和角膜上皮屏障破坏。在老年Itpr2-/-;Itpr3-/-小鼠中还检测到泪腺中有炎性细胞浸润以及血清自身抗体升高，血清自身抗体升高是人类干燥综合征（SS）的一个代表性标志物。这些结果表明，IP3R对于副交感神经和交感神经通路中的泪液分泌至关重要，并且Itpr2-/-;Itpr3-/-小鼠可能是一种新的干眼小鼠模型，其症状类似于SS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/ee594612b2c6/pone.0099205.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/4f9e5365c2d2/pone.0099205.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/867bd34f9913/pone.0099205.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/aef8c0d392b2/pone.0099205.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/376fbae3fdca/pone.0099205.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/565c8ee15328/pone.0099205.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/ee594612b2c6/pone.0099205.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/4f9e5365c2d2/pone.0099205.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/867bd34f9913/pone.0099205.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/aef8c0d392b2/pone.0099205.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/376fbae3fdca/pone.0099205.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/565c8ee15328/pone.0099205.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9753/4047094/ee594612b2c6/pone.0099205.g006.jpg

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