Alzheimer’s disease is characterized by the aberrant deposition of protein in the brain and is the leading cause of dementia worldwide. Increasingly, there have been reports of the presence of these protein hallmarks in the retina. In this study, we assayed the retina of 5xFAD mice, a transgenic model of amyloid deposition known to exhibit dementia-like symptoms with age. Using OCT, we found that the retinal nerve fiber layer was thinner in 5xFAD at 6, 12, and 17 months of age compared with wild-type littermates, but the inner plexiform layer was thicker at 6 months old. Retinal function showed reduced ganglion cell responses to light in 5xFAD at 6, 12, and 17 months of age. This functional loss was observed in the outer retina at 17 months of age but not in younger mice. We showed using immunohistochemistry and ELISA that soluble and insoluble amyloid was present in the retina and brain at all ages. In conclusion, we report that amyloid is present in brain and retina of 5xFAD mice and that the pattern of neuronal dysfunction occurs in the inner retina at the early ages and progresses to encompass the outer retina with age. This implies that the inner retina is more sensitive to amyloid changes in early disease and that the outer retina is also affected with disease progression.

中文翻译：

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阿尔茨海默病 5xFAD 小鼠模型的视网膜功能和结构变化

阿尔茨海默病的特征是蛋白质在大脑中的异常沉积，是全世界痴呆症的主要原因。越来越多的报道称视网膜中存在这些蛋白质标志。在这项研究中，我们分析了 5xFAD 小鼠的视网膜，这是一种淀粉样蛋白沉积的转基因模型，已知随着年龄的增长会出现痴呆样症状。使用 OCT，我们发现在 6、12 和 17 个月大的 5xFAD 中，与野生型同窝仔相比，视网膜神经纤维层更薄，但在 6 个月大时内丛状层更厚。视网膜功能显示，在 6、12 和 17 个月大的 5xFAD 中，神经节细胞对光的反应降低。这种功能丧失在 17 个月大的外层视网膜中观察到，但在年轻小鼠中未观察到。我们使用免疫组织化学和 ELISA 表明，所有年龄段的视网膜和大脑中都存在可溶性和不溶性淀粉样蛋白。总之，我们报告淀粉样蛋白存在于 5xFAD 小鼠的大脑和视网膜中，并且神经元功能障碍的模式发生在早期的内层视网膜中，并随着年龄的增长逐渐包括外层视网膜。这意味着内层视网膜对早期疾病的淀粉样蛋白变化更敏感，外层视网膜也受到疾病进展的影响。