Lim Jeremiah K H, Li Qiao-Xin, He Zheng, Vingrys Algis J, Chinnery Holly R, Mullen Jamie, Bui Bang V, Nguyen Christine T O
Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, Australia.
Optometry and Vision Science, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.
Front Neurosci. 2020 Aug 13;14:862. doi: 10.3389/fnins.2020.00862. eCollection 2020.
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.
阿尔茨海默病的特征是大脑中蛋白质异常沉积，是全球痴呆症的主要病因。越来越多的报道称视网膜中存在这些蛋白质特征。在本研究中，我们检测了5xFAD小鼠的视网膜，5xFAD小鼠是一种已知随着年龄增长会出现类似痴呆症状的淀粉样蛋白沉积转基因模型。使用光学相干断层扫描（OCT），我们发现，与野生型同窝小鼠相比，5xFAD小鼠在6、12和17月龄时视网膜神经纤维层更薄，但在6月龄时内网状层更厚。视网膜功能显示，5xFAD小鼠在6、12和17月龄时神经节细胞对光的反应降低。这种功能丧失在17月龄的小鼠外视网膜中观察到，但在较年轻的小鼠中未观察到。我们通过免疫组织化学和酶联免疫吸附测定（ELISA）表明，可溶性和不溶性淀粉样蛋白在所有年龄段的视网膜和大脑中均存在。总之，我们报告5xFAD小鼠的大脑和视网膜中存在淀粉样蛋白，并且神经元功能障碍模式在早期发生于内视网膜，并随着年龄增长扩展至外视网膜。这意味着内视网膜在疾病早期对淀粉样蛋白变化更敏感，并且外视网膜也会随着疾病进展而受到影响。
