Buchanan Ocular Therapeutics Unit, Department of Ophthalmology and the New Zealand National Eye Centre, University of Auckland, New Zealand.
Department of Ophthalmology and the New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
Ageing Res Rev. 2023 Jul;88:101954. doi: 10.1016/j.arr.2023.101954. Epub 2023 May 13.
With increasing age, structural changes occur in the eye and brain. Neuronal death, inflammation, vascular disruption, and microglial activation are among many of the pathological changes that can occur during ageing. Furthermore, ageing individuals are at increased risk of developing neurodegenerative diseases in these organs, including Alzheimer's disease (AD), Parkinson's disease (PD), glaucoma and age-related macular degeneration (AMD). Although these diseases pose a significant global public health burden, current treatment options focus on slowing disease progression and symptomatic control rather than targeting underlying causes. Interestingly, recent investigations have proposed an analogous aetiology between age-related diseases in the eye and brain, where a process of chronic low-grade inflammation is implicated. Studies have suggested that patients with AD or PD are also associated with an increased risk of AMD, glaucoma, and cataracts. Moreover, pathognomonic amyloid-β and α-synuclein aggregates, which accumulate in AD and PD, respectively, can be found in ocular parenchyma. In terms of a common molecular pathway that underpins these diseases, the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome is thought to play a vital role in the manifestation of all these diseases. This review summarises the current evidence regarding cellular and molecular changes in the brain and eye with age, similarities between ocular and cerebral age-related diseases, and the role of the NLRP3 inflammasome as a critical mediator of disease propagation in the eye and the brain during ageing.
随着年龄的增长，眼睛和大脑会发生结构变化。神经元死亡、炎症、血管破裂和小胶质细胞激活等是衰老过程中可能发生的许多病理变化之一。此外，衰老个体在这些器官中患神经退行性疾病的风险增加，包括阿尔茨海默病（AD）、帕金森病（PD）、青光眼和年龄相关性黄斑变性（AMD）。尽管这些疾病对全球公共卫生造成了重大负担，但目前的治疗选择侧重于减缓疾病进展和症状控制，而不是针对根本原因。有趣的是，最近的研究提出了眼睛和大脑中与年龄相关疾病之间类似的病因，其中涉及慢性低度炎症过程。研究表明，AD 或 PD 患者也与 AMD、青光眼和白内障的风险增加相关。此外，分别在 AD 和 PD 中积累的标志性淀粉样蛋白-β和α-突触核蛋白聚集物可以在眼部实质中发现。就支持这些疾病的共同分子途径而言，核苷酸结合域、富含亮氨酸重复家族和吡喃结构域包含蛋白 3（NLRP3）炎性小体被认为在所有这些疾病的表现中起着至关重要的作用。这篇综述总结了目前关于大脑和眼睛随年龄变化的细胞和分子变化、眼部和脑部与年龄相关疾病的相似性以及 NLRP3 炎性小体作为衰老过程中眼部和大脑中疾病传播的关键介质的作用的证据。
