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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,锥形和黑色素光电传导信号通路缺乏原理成分的小鼠视网膜中光反应的表征

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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-fos expression 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-fos expression is evident in the TKO retina, with c-fos expression 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)小鼠缺乏杆,锥体和光敏视网膜神经节细胞(PRGCS)中存在的光调节信号通路的基本组分,因此预计缺乏对光的所有敏感性。然而,许多研究表明,在这些小鼠中持续存在光反应。在该研究中,我们使用多电极阵列(MEA)记录和光诱导的C-FOS表达,以进一步表征TKO视网膜的光反应。在MEA记录期间,在MEA记录期间常规检测到小,但坚固的电气图仪型响应,具有与杆驱动响应一致的性质。此外,在TKO视网膜中,在TKO视网膜中显而易见的光学诱导的C-FOS表达模式,C-FOS表达在很大程度上限于表达残疾-1(DAB1)但缺乏甘氨酸转运蛋白转运蛋白转运蛋白的表达的小子集(GLYT-1)。集体这些数据与TKO视网膜中的新型光感测途径的持续存在一致,其源于杆光感受器,可能是具有不同功能特性的罕见棒子集,并且其繁殖至AII氨基细胞的非典型亚型。此外,uV光刺激后观察到的最小反应仅表明非视觉OPSIN OPN5在驱动小鼠视网膜内的兴奋性光反应方面的有限作用。

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