Profound defects in pupillary responses to light in TRPM-channel null mice: a role for TRPM channels in non-image-forming photoreception.
Profound defects in pupillary responses to light in TRPM-channel null mice: a role for TRPM channels in non-image-forming photoreception.
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DOI：
10.1111/j.1460-9568.2011.07944.x
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Peirson SN
中科院分区：
文献类型：
--
作者：
Hughes S;Pothecary CA;Jagannath A;Foster RG;Hankins MW;Peirson SN
TRPM 1是一种自发活性的非选择性阳离子通道，最近已被证明在ON双极细胞的去偏振光响应中发挥重要作用。与此作用一致，TRPM 1基因突变已被确定为先天性静止性夜盲症的主要原因。然而，以前的微阵列研究表明，Trpm 1和Trpm 3是急性调节缺乏杆和锥（rd/rd cl）的小鼠眼睛的光，一个发现与非图像形成光感受的作用一致。在这项研究中，我们发现Trpm 1 −/−和Trpm 3 −/−动物的瞳孔光反应显著减弱。Trpm 1 −/−小鼠在瞳孔反应方面表现出严重的缺陷，远远超过在缺乏视杆细胞和视锥细胞（rd/rd cl）或黑视蛋白的小鼠中观察到的缺陷，并且不能单独用双极细胞功能缺陷来解释。免疫定位研究表明，TRPM 1在ON双极细胞中表达，也在神经节细胞层中的细胞亚群中表达，包括表达黑视素的光敏视网膜神经节细胞（pRGC）。我们的结论是，除了其在双极细胞信号传导的作用，TRPM 1参与非图像形成光的反应，并可能在pRGC内执行功能的作用。相比之下，TRPM 3 −/−小鼠表现出更微妙的瞳孔表型，在明亮的光线和昏暗的光线条件下反应减弱。在Muller细胞和睫状体中检测到TRPM 3的表达，但在pRGC中不存在，因此我们的数据支持TRPM 3在瞳孔光反应中的间接作用。
TRPM1 is a spontaneously active non-selective cation channel that has recently been shown to play an important role in the depolarising light responses of ON bipolar cells. Consistent with this role, mutations in the TRPM1 gene have been identified as a principle cause of congenital stationary night blindness. However, previous microarray studies have shown that Trpm1 and Trpm3 are acutely regulated by light in the eye of mice lacking rods and cones (rd/rd cl), a finding consistent with a role in non-image forming photoreception. In this study we show that pupillary light responses are significantly attenuated in both Trpm1−/− and Trpm3−/− animals. Trpm1−/− mice exhibit a profound deficit in the pupillary response that is far in excess of that observed in mice lacking rods and cones (rd/rd cl) or melanopsin, and cannot be explained by defects in bipolar cell function alone. Immunolocalisation studies suggest that TRPM1 is expressed in ON-bipolar cells and also a subset of cells in the ganglion cell layer, including melanopsin expressing photosensitive retinal ganglion cells (pRGCs). We conclude that in addition to its role in bipolar cell signalling, TRPM1 is involved in non-image forming responses to light and may perform a functional role within pRGCs. By contrast, TRPM3−/− mice display a more subtle pupillary phenotype with attenuated responses under bright light and dim light conditions. Expression of TRPM3 is detected in Muller cells and the ciliary body but is absent from pRGCs, and thus our data supports an indirect role for TRPM3 in pupillary light responses.
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影响因子：
33.6
作者：
Do MT;Yau KW
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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