Dai Xufeng, Zhang Hua, He Ying, Qi Yan, Chang Bo, Pang Ji-jing
Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China; Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China.
PLoS One. 2015 Feb 23;10(2):e0117570. doi: 10.1371/journal.pone.0117570. eCollection 2015.
Early studies on Rpe65 knockout mice reported that remaining visual function was attributable to cone function. However, this finding has been challenged more and more as time has passed. Electroretinograms (ERGs) showed that rd12 mice, a spontaneous animal model of RPE65 Leber's congenital amaurosis, had sizeable photopic responses. Unfortunately, the recorded ERG waveform was difficult to interpret because of a remarkably delayed peak-time, which resembles a rod response more than a cone response. Here, we compare flicker ERGs in animals with normal rod and cone function (C57BL/6J mice), pure rod function (cpfl5 mice), and pure cone function (Rho(-/-) mice) under different adaptation levels and stimulus intensities. These responses were then compared with those obtained from rd12 mice. Our results showed that normal rods respond to low frequency flicker (5 and 15 Hz) and that normal cones respond to both low and high frequency flicker (5-35 Hz). As was seen in cpfl5 mice, rd12 mice had recordable responses to low frequency flicker (5 and 15Hz), but not to high frequency flicker (25 and 35 Hz). We hypothesize that abnormal rods may be the source of residual vision in rd12 mice, which is proved correct here with double mutant rd12mice. In this study, we show, for the first time, that frequency-response ERGs can effectively distinguish cone- and rod-driven responses in the rd12 mouse. It is another simple and valid method for evaluating the respective contributions of retinal rods and cones.
早期对Rpe65基因敲除小鼠的研究报告称，剩余的视觉功能归因于视锥细胞功能。然而，随着时间的推移，这一发现受到了越来越多的质疑。视网膜电图（ERG）显示，rd12小鼠是RPE65型莱伯先天性黑蒙的自发动物模型，具有相当大的明视觉反应。不幸的是，由于峰值时间显著延迟，记录的ERG波形难以解释，这种波形更类似于视杆细胞反应而非视锥细胞反应。在这里，我们比较了在不同适应水平和刺激强度下，具有正常视杆和视锥细胞功能的动物（C57BL/6J小鼠）、纯视杆细胞功能的动物（cpfl5小鼠）和纯视锥细胞功能的动物（Rho(-/-)小鼠）的闪烁ERG。然后将这些反应与从rd12小鼠获得的反应进行比较。我们的结果表明，正常视杆细胞对低频闪烁（5和15Hz）有反应，正常视锥细胞对低频和高频闪烁（5-35Hz）均有反应。正如在cpfl5小鼠中所见，rd12小鼠对低频闪烁（5和15Hz）有可记录的反应，但对高频闪烁（25和35Hz）没有反应。我们假设异常视杆细胞可能是rd12小鼠残余视力的来源，这在双突变rd12小鼠中得到了证实。在本研究中，我们首次表明，频率响应ERG可以有效区分rd12小鼠中视锥细胞和视杆细胞驱动的反应。这是另一种评估视网膜视杆细胞和视锥细胞各自贡献的简单有效的方法。
