Volland Stefanie, Esteve-Rudd Julian, Hoo Juyea, Yee Claudine, Williams David S
Departments of Ophthalmology and Neurobiology, Stein Eye Institute, Molecular Biology Institute, Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.
PLoS One. 2015 Apr 29;10(4):e0125631. doi: 10.1371/journal.pone.0125631. eCollection 2015.
Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.
小鼠模型极大地帮助了我们对视网膜变性的理解。然而，小鼠视网膜没有黄斑，这就引发了一个问题：小鼠是否是黄斑变性的相关模型。在本研究中，对小鼠中央视网膜和人类黄斑的组织结构进行了定量比较，重点关注了一些被认为在使黄斑易受导致变性的压力影响方面很重要的结构特征：光感受器密度、视网膜色素上皮（RPE）上的吞噬负荷以及布鲁赫膜的相对薄度。来自两种小鼠品系视网膜的光镜和电镜测量数据，以及已发表的关于人类视网膜的数据，被用于计算和后续比较。与人类视网膜一样，小鼠视网膜的中央区域比周边区域具有更高的光感受器细胞密度和更薄的布鲁赫膜；然而，这些从周边到中央的梯度幅度在人类中更大。可能更相关的是实际的光感受器细胞密度，小鼠中央视网膜的光感受器细胞密度比人类黄斑中的要大得多，这使得小鼠RPE的吞噬负荷更高。此外，在对应于人类黄斑外周一半的偏心度处，小鼠和人类的视杆细胞与视锥细胞比例相似。因此，就光感受器密度和RPE的吞噬负荷而言，小鼠中央视网膜至少模拟了黄斑更外周的部分，而黄斑变性通常首先在该部位显现。
