Transient receptor potential cation channel subfamily V member 1 expressing corneal sensory neurons can be subdivided into at least three subpopulations
Transient receptor potential cation channel subfamily V member 1 expressing corneal sensory neurons can be subdivided into at least three subpopulations
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DOI：
10.3389/fnana.2015.00071
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发表时间：
2015-06-08
影响因子：
2.9
通讯作者：
Ivanusic, Jason J.
中科院分区：
文献类型：
--
作者：
Alamri, Abdulhakeem;Bron, Romke;Ivanusic, Jason J.
角膜由三种主要的感觉神经元支配：多模伤害感受器、纯机械伤害感受器和冷感觉神经元。本文研究了瞬时受体电位阳离子通道亚家族V成员1 （TRPV1）在豚鼠角膜感觉神经元中的表达，TRPV1是一种广泛使用的多模态伤害感受器分子标志物。我们采用逆行示踪方法鉴定三叉神经节（TG）中的角膜传入神经元，并采用双标记原位杂交和/或免疫组织化学方法确定其分子谱。此外，我们利用免疫组织化学揭示了角膜上皮中表达TRPV1的神经末梢的神经化学和结构。大约45%的角膜传入神经元表达TRPV1, 28%表达Piezo2（推测为纯机械伤害感受器的标记），8%表达瞬时受体电位阳离子通道亚家族M成员8 （TRPM8，冷感神经元的标记）。TRPV1和Piezo2在角膜传入神经元中无共表达，而TRPV1神经元中有6%共表达TRPM8。根据降钙素基因相关肽（CGRP）和/或胶质细胞系源性神经营养因子家族受体α 3 （GFR α 3）的共表达，将表达TRPV1的角膜传入神经元分为三个亚群。在角膜上皮中，共同表达CGRP和GFR α 3的TRPV1轴突在翼细胞层中以简单的未分枝末梢死亡。相比之下，仅共表达GFR α 3的细胞具有分支末梢，分支末梢位于鳞状细胞层，而仅共表达CGRP的细胞在基底上皮中具有简单末梢。本研究表明，大多数表达TRPV1的角膜传入神经元（约90%）可能是多模态伤害感受器。此外，根据表达TRPV1的角膜传入神经元的分子表型、神经末梢形态和在角膜上皮中的分布，可以将其细分为特定的亚群。
The cornea is innervated by three main functional classes of sensory neurons: polymodal nociceptors, pure mechano-nociceptors and cold-sensing neurons. Here we explored transient receptor potential cation channel subfamily V member 1 (TRPV1) expression in guinea pig corneal sensory neurons, a widely used molecular marker of polymodal nociceptors. We used retrograde tracing to identify corneal afferent neurons in the trigeminal ganglion (TG) and double label in situ hybridization and/or immunohistochemistry to determine their molecular profile. In addition, we used immunohistochemistry to reveal the neurochemistry and structure of TRPV1 expressing nerve endings in the corneal epithelium. Approximately 45% of corneal afferent neurons expressed TRPV1, 28% expressed Piezo2 (a marker of putative pure mechano-nociceptors) and 8% expressed the transient receptor potential cation channel subfamily M member 8 (TRPM8; a marker of cold-sensing neurons). There was no co-expression of TRPV1 and Piezo2 in corneal afferent neurons, but 6% of TRPV1 neurons co-expressed TRPM8. The TRPV1 expressing corneal afferent neurons could be divided into three subpopulations on the basis of calcitonin gene-related peptide (CGRP) and/or or glial cell line-derived neurotrophic factor family receptor alpha3 (GFR alpha 3) co-expression. In the corneal epithelium, the TRPV1 axons that co-expressed CGRP and GFR alpha 3 ded as simple unbranched endings in the wing cell layer. In contrast, those that only co-expressed GFR alpha 3 had ramifying endings that branched and terminated in the squamous cell layer, whereas those that only co-expressed CGRP had simple endings in the basal epithelium. This study shows that the majority of TRPV1 expressing corneal afferent neurons (>90%) are likely to be polymodal nociceptors. Furthermore, TRPV1 expressing corneal afferent neurons can be subdivided into specific subpopulations based on their molecular phenotype, nerve terminal morphology and distribution in the corneal epithelium.