Identification and Pathology of a Macula-Related Structure in the Mouse Eye

项目摘要/摘要 黄斑部疾病是一种灵长类特有的视网膜特化，对高视力至关重要，是一种 全球范围内导致视力丧失的主要原因。动物模型是解决黄斑疾病的关键 机制和试验治疗。非人灵长类动物，它们被认为是模型，因为它们 拥有黄斑，需要几十年的时间才能形成，维护费用也很高。狗和猪也被 被认为是黄斑相关结构，概括了黄斑疾病的特征，已有报道。 只有在狗身上，对这些动物的研究也受到时间和成本的限制。实验室的小鼠可以被培育和 分析效率比大型动物高得多，但它们在黄斑疾病研究中的使用经常受到批评 由于认为老鼠缺乏与斑疹相关的结构。在挑战这一观点的初步研究中，提出了 CtnNA1纯合子突变小鼠模型视网膜色素上皮(RPE)的透明损伤 蝶形色素营养不良呈时间偏向分布于背带。一条相似的带子 在杂合子CtnNA1突变的眼底图像中，可以观察到RPE中或附近的细微病变随年龄增长而变化 老鼠，它们的病情较轻。这种分布与小鼠视网膜的背侧-颞叶特征相平行。 以感光细胞和神经节细胞密度梯度为特征的，如人类黄斑。中环 假说是小鼠后眼球的这一区域构成了与黄斑相关的视网膜特化 在与人类黄斑疾病有关的条件下发生损害。为了检验这一假设，我们将1) 测定CtnNA1纯合子突变小鼠视网膜色素上皮损伤的局部分布 这些病变附近的视网膜结构，以及相应的RPE和视网膜结构 通过非侵入性成像和显微镜检查野生型小鼠的区域；以及2)检查是否存在微小的RPE损害 在老化的杂合子CtnNA1突变体和野生型小鼠中出现类似的地形分布。至 为了达到这些目的，我们将使用一种新的方法在球面上配准小鼠的后眼图像 基于血管地标的几何学。这些研究预计将定义与黄斑相关的结构 以基因和年龄相关的致病过程为靶点的小鼠。 好了！

PROJECT SUMMARY/ABSTRACT Diseases of the macula, a primate-specific retinal specialization that is critical for high acuity vision, are a leading cause of vision loss worldwide. Animal models are essential for resolving macular disease mechanisms and testing treatments. Non-human primates, which are favored as models because they possess a macula, require decades to develop and are costly to maintain. Dogs and pigs have also been considered, but a macula-related structure that recapitulates features of macular disease has been reported only in dogs, and studies of these animals are also limited by time and cost. Laboratory mice can be bred and analyzed much more efficiently than large animals, but their use in macular disease research is often criticized due to the view that mice lack a macula-related structure. In preliminary studies that challenge this view, raised hyaline lesions in the retinal pigment epithelium (RPE) of a homozygous mutant Ctnna1 mouse model of butterfly-shaped pigment dystrophy were distributed in a dorsal band with a temporal bias. A similar band of subtle lesions in or near the RPE was observed with age in fundus images of heterozygous Ctnna1 mutant mice, which have milder disease. This distribution parallels a dorsal-temporal feature of the mouse retina characterized by photoreceptor and ganglion cell density gradients, as in the human macula. The central hypothesis is that this area of the mouse posterior eye constitutes a macula-related retinal specialization that develops lesions under conditions linked to human macular disease. To test this hypothesis, we will 1) determine the topographic distribution of hyaline RPE lesions in homozygous Ctnna1 mutant mice, the structure of the retina in the vicinity of these lesions, and the RPE and retinal structure of the corresponding region in wild-type mice by noninvasive imaging and microscopy; and 2) examine whether subtle RPE lesions occur with a similar topographic distribution in aging heterozygous Ctnna1 mutants and in wild-type mice. To achieve these aims, we will use a new approach to register images of the mouse posterior eye in spherical geometry based on vascular landmarks. These studies are expected to define a macula-related structure in mice that is targeted by gene- and age-dependent pathogenic processes. !