PDF(Pubmed)
Abstract：
In this work, we introduce a diurnal rodent, the Mongolian gerbil (Meriones unguiculatus) (MG) as an alternative to study retinal cone system physiology and pathophysiology in mice. The cone system is of particular importance, as it provides high-acuity and color vision and its impairment in retinal disorders is thus especially disabling. Despite their nocturnal lifestyle, mice are currently the most popular animals to study cone-related diseases due to the high availability of genetically modified models. However, the potential for successful translation of any cone-related results is limited due to the substantial differences in retinal organization between mice and humans. Alternatively, there are diurnal rodents such as the MG with a higher retinal proportion of cones and a macula-like specialized region for improved visual resolution, the visual streak. The focus of this work was the evaluation of the MG\'s cone system functionality using full-field electroretinography (ERG), together with a morphological assessment of its retinal/visual streak organization via angiography, optical coherence tomography (OCT), and photoreceptor immunohistochemistry. We found that rod system responses in MGs were comparable or slightly inferior to mice, while in contrast, cone system responses were much larger, more sensitive, and also faster than those in the murine counterparts, and in addition, it was possible to record sizeable ON and OFF ERG components. Morphologically, MG cone photoreceptor opsins were evenly distributed throughout the retina, while mice show a dorsoventral M- and S-opsin gradient. Additionally, each cone expressed a single opsin, in contrast to the typical co-expression of opsins in mice. Particular attention was given to the visual streak region, featuring a higher density of cones, elongated cone and rod outer segments (OSs), and an increased thickness of the inner and outer retinal layers in comparison to peripheral regions. In summary, our data render the MG a supreme model to investigate cone system physiology, pathophysiology, and to validate potential therapeutic strategies in that context.
摘要：
在这项工作中,我们介绍一种昼夜啮齿动物，蒙古沙鼠（Merionesunguiculatus）（MG）作为研究小鼠视网膜视锥系统生理学和病理生理学的替代方法。圆锥系统特别重要，因为它提供高敏锐度和彩色视觉，并且其在视网膜疾病中的损害因此特别是致残。尽管他们的夜间生活方式，由于转基因模型的高度可用性，小鼠目前是研究视锥细胞相关疾病的最受欢迎的动物。然而,由于小鼠和人类之间视网膜组织的显著差异,成功翻译任何视锥相关结果的潜力是有限的.或者，有昼夜啮齿动物，如MG，具有较高的视锥视网膜比例和黄斑样专门区域，以提高视觉分辨率，视觉条纹。这项工作的重点是使用全场视网膜电图（ERG）评估MG的视锥系统功能，通过血管造影对其视网膜/视觉条纹组织进行形态学评估，光学相干断层扫描(OCT),和光感受器免疫组织化学。我们发现MGs中的杆系统反应与小鼠相当或略逊一筹，而相比之下，锥体系统的响应要大得多，更敏感,也比鼠类的速度快，此外,可以记录相当大的ON和OFFERG组件。形态学上,MG视锥感光体在整个视网膜上均匀分布，而小鼠显示背腹侧M-和S-视蛋白梯度。此外,每个视锥表达一个视蛋白，与小鼠视蛋白的典型共表达相反。特别注意视觉条纹区域，具有更高密度的锥体，细长锥形和杆外部段(OS)，与周边区域相比，视网膜内层和外层的厚度增加。总之,我们的数据使MG成为研究视锥系统生理学的最高模型，病理生理学,并在这种情况下验证潜在的治疗策略。
