Flinders Centre for Ophthalmology, Eye and Vision Research, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Adelaide, Australia.
SAHMRI Bioinformatics Core, South Australian Health and Medical Research Institute, Adelaide, Australia.
Invest Ophthalmol Vis Sci. 2022 Mar 2;63(3):26. doi: 10.1167/iovs.63.3.26.
Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research.
Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets.
Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated.
This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.
假性剥脱综合征（PEX）是一种常见的全身性疾病，可导致严重且常不可逆的视力丧失。尽管进行了大量研究，但 PEX 的发病机制仍不完全清楚。本研究旨在进行首次 RNAseq 研究，阐明 PEX 的病理生理学，并为未来的研究提供一个公开的转录组学数据资源。
从 25 名接受白内障手术的 PEX 患者和 39 名非 PEX 对照者的人眼晶状体囊上皮样本中提取 RNA。对这些标本进行多聚腺苷酸化（mRNA）选择和深度批量 RNA 测序。差异表达分析研究了蛋白质编码基因转录本。探索性分析使用了途径分析工具以及经过整理的类和疾病特异性基因集。
差异表达分析表明，根据 PEX 状态，有 2882 个基因表达差异。与病毒基因表达途径相关的基因是上调最明显的基因之一，同时还包括编码核糖体和线粒体呼吸转运链蛋白的基因。细胞黏附蛋白转录本，包括 4 型胶原亚基，下调。
该比较转录组数据集突出了 PEX 中的新的和以前认识到的致病途径，并提供了首个全面的转录组学资源，为进一步了解 PEX 病理生理学增加了一个层面。
