Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Int J Mol Sci. 2021 Feb 26;22(5):2360. doi: 10.3390/ijms22052360.
Amyloid-β (Aβ) accumulations have been identified in the retina for neurodegeneration-associated disorders like Alzheimer's disease (AD), glaucoma, and age-related macular degeneration (AMD). Elevated retinal Aβ levels were associated with progressive retinal neurodegeneration, elevated cerebral Aβ accumulation, and increased disease severity with a decline in cognition and vision. Retinal Aβ accumulation and its pathological effects were demonstrated to occur prior to irreversible neurodegeneration, which highlights its potential in early disease detection and intervention. Using the retina as a model of the brain, recent studies have focused on characterizing retinal Aβ to determine its applicability for population-based screening of AD, which warrants a further understanding of how Aβ manifests between these disorders. While current treatments directly targeting Aβ accumulations have had limited results, continued exploration of Aβ-associated pathological pathways may yield new therapeutic targets for preserving cognition and vision. Here, we provide a review on the role of retinal Aβ manifestations in these distinct neurodegeneration-associated disorders. We also discuss the recent applications of retinal Aβ for AD screening and current clinical trial outcomes for Aβ-associated treatment approaches. Lastly, we explore potential future therapeutic targets based on overlapping mechanisms of pathophysiology in AD, glaucoma, and AMD.
淀粉样蛋白-β（Aβ）在与神经退行性疾病相关的视网膜中积累，如阿尔茨海默病（AD）、青光眼和年龄相关性黄斑变性（AMD）。视网膜 Aβ 水平升高与进行性视网膜神经退行性变、大脑 Aβ 积累增加以及认知和视力下降导致的疾病严重程度增加有关。视网膜 Aβ 积累及其病理作用在不可逆转的神经退行性变之前就已发生，这突出了其在早期疾病检测和干预中的潜力。利用视网膜作为大脑的模型，最近的研究集中在表征视网膜 Aβ 上，以确定其在 AD 的人群筛查中的适用性，这需要进一步了解 Aβ 在这些疾病之间的表现方式。虽然目前直接针对 Aβ 积累的治疗方法效果有限，但对 Aβ 相关病理途径的持续探索可能为保护认知和视力提供新的治疗靶点。在这里，我们综述了视网膜 Aβ 表现在这些不同的与神经退行性疾病相关的疾病中的作用。我们还讨论了视网膜 Aβ 在 AD 筛查中的最新应用以及 Aβ 相关治疗方法的当前临床试验结果。最后，我们探讨了基于 AD、青光眼和 AMD 中重叠的病理生理学机制的潜在未来治疗靶点。
