PDF(Pubmed)
Abstract：
Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNAseq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.
摘要：
由视网膜神经退行性病变引起的与年龄相关的视力丧失在我们的老龄化社会中变得越来越普遍。了解衰老对视网膜稳态的生理和分子影响，我们用了短命的非洲绿松石小鱼，一种已知会自然发展中枢神经系统（CNS）衰老标志和视力丧失的模型。三个年龄组（6-，12-，和18周龄）确定了killifish视网膜中的转录老化指纹，在老年大脑中也发现了揭示的途径，包括氧化应激,胶质增生,和发炎。这些发现与衰老小鼠视网膜中的观察结果相当。此外,与视网膜疾病相关的基因的转录变化，如青光眼和年龄相关性黄斑变性，被观察到。Kurlifish视网膜的细胞异质性被表征，确认所有典型脊椎动物视网膜细胞类型的存在。批量和scRNAseq实验之间的年龄匹配样本的数据整合显示，衰老后基因表达的细胞特异性丧失。提示转录稳态的潜在破坏。鉴定的细胞类型中的差异表达分析强调了神经胶质/免疫细胞作为衰老过程中重要的应激调节因子的作用。我们的工作强调了快速衰老的killifish在阐明与年龄相关的视网膜疾病和视力下降的分子特征方面的价值。这项研究有助于理解与年龄相关的分子通路变化如何影响中枢神经系统健康。提供的见解，可以为未来的治疗策略的年龄相关的病理。
