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Characterisation of light responses in the retina of mice lacking principle components of rod, cone and melanopsin phototransduction signalling pathways

机译:缺乏杆,视锥细胞和黑视蛋白光转导信号传导途径主要成分的小鼠视网膜的光反应特性

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摘要

Gnat−/−, Cnga3−/−, Opn4−/− triple knockout (TKO) mice lack essential components of phototransduction signalling pathways present in rods, cones and photosensitive retinal ganglion cells (pRGCs), and are therefore expected to lack all sensitivity to light. However, a number of studies have shown that light responses persist in these mice. In this study we use multielectrode array (MEA) recordings and light-induced c-fosexpression to further characterise the light responses of the TKO retina. Small, but robust electroretinogram type responses are routinely detected during MEA recordings, with properties consistent with rod driven responses. Furthermore, a distinctive pattern of light-induced c-fosexpression is evident in the TKO retina, with c-fosexpression largely restricted to a small subset of amacrine cells that express disabled-1 (Dab1) but lack expression of glycine transporter-1 (GlyT-1). Collectively these data are consistent with the persistence of a novel light sensing pathway in the TKO retina that originates in rod photoreceptors, potentially a rare subset of rods with distinct functional properties, and which is propagated to an atypical subtype of AII amacrine cells. Furthermore, the minimal responses observed following UV light stimulation suggest only a limited role for the non-visual opsin OPN5 in driving excitatory light responses within the mouse retina.
机译:Gnat-/-,Cnga3-/-,Opn4-/-三重敲除(TKO)小鼠缺乏视杆,视锥细胞和光敏性视网膜神经节细胞(pRGC)中存在的光转导信号通路的基本组成部分,因此预期对它们缺乏全部敏感性光。但是,许多研究表明,这些小鼠中仍然存在光反应。在这项研究中,我们使用多电极阵列(MEA)记录和光诱导的c-fosexpression来进一步表征TKO视网膜的光响应。在MEA记录期间,通常会检测到小而健壮的视网膜电图类型响应,其特性与棒驱动响应一致。此外,在TKO视网膜中明显存在光诱导的c-fos表达的独特模式,其中c-fos表达主要限于表达disabled-1(Dab1)但缺乏甘氨酸转运蛋白1(GlyT)的一小部分无长突细胞。 -1)。总的来说,这些数据与TKO视网膜中新的光感测路径的持久性相一致,该光敏性路径起源于视杆感光器,这可能是罕见的具有不同功能特性的视杆的子集,并传播到非典型的AII无长突细胞亚型。此外,紫外线刺激后观察到的最小反应表明,非视觉视蛋白OPN5在驱动小鼠视网膜内的兴奋性光反应中仅发挥有限的作用。

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