Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
J Mol Neurosci. 2024 Aug 7;74(3):74. doi: 10.1007/s12031-024-02249-9.
Age-related macular degeneration (AMD) is one of the most common causes of irreversible vision loss in the elderly. Its pathogenesis is likely multifactorial, involving a complex interaction of metabolic and environmental factors, and remains poorly understood. Previous studies have shown that mitochondrial dysfunction and oxidative stress play a crucial role in the development of AMD. Oxidative damage to the retinal pigment epithelium (RPE) has been identified as one of the major mediators in the pathogenesis of age-related macular degeneration (AMD). Therefore, this article combines transcriptome sequencing (RNA-seq) and single-cell sequencing (scRNA-seq) data to explore the role of mitochondria-related genes (MRGs) in AMD. Firstly, differential expression analysis was performed on the raw RNA-seq data. The intersection of differentially expressed genes (DEGs) and MRGs was performed. This paper proposes a deep subspace nonnegative matrix factorization (DS-NMF) algorithm to perform a multi-layer nonlinear transformation on the intersection of gene expression profiles corresponding to AMD samples. The age of AMD patients is used as prior information at the network's top level to change the data distribution. The classification is based on reconstructed data with altered distribution. The types obtained significantly differ in scores of multiple immune-related pathways and immune cell infiltration abundance. Secondly, an optimal AMD diagnosis model was constructed using multiple machine learning algorithms for external and qRT-PCR verification. Finally, ten potential therapeutic drugs for AMD were identified based on cMAP analysis. The AMD subtypes identified in this article and the diagnostic model constructed can provide a reference for treating AMD and discovering new drug targets.
年龄相关性黄斑变性（AMD）是老年人不可逆视力丧失的最常见原因之一。其发病机制可能是多因素的，涉及代谢和环境因素的复杂相互作用，目前仍知之甚少。先前的研究表明，线粒体功能障碍和氧化应激在 AMD 的发展中起着关键作用。视网膜色素上皮（RPE）的氧化损伤已被确定为年龄相关性黄斑变性（AMD）发病机制中的主要介质之一。因此，本文结合转录组测序（RNA-seq）和单细胞测序（scRNA-seq）数据，探讨了与线粒体相关的基因（MRGs）在 AMD 中的作用。首先，对原始 RNA-seq 数据进行差异表达分析。对差异表达基因（DEGs）和 MRGs 进行了交集分析。本文提出了一种深度子空间非负矩阵分解（DS-NMF）算法，对 AMD 样本基因表达谱的交集进行多层次非线性变换。AMD 患者的年龄作为网络顶层的先验信息，改变数据分布。分类基于分布改变的重建数据进行。基于多种免疫相关通路和免疫细胞浸润丰度的评分，所获得的类型差异显著。其次，使用多种机器学习算法构建了最佳 AMD 诊断模型，进行外部和 qRT-PCR 验证。最后，基于 cMAP 分析鉴定了 10 种潜在的 AMD 治疗药物。本文鉴定的 AMD 亚型和构建的诊断模型可为治疗 AMD 和发现新的药物靶点提供参考。
