Ophthalmology Department of QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Otolaryngology Department of QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
BMC Med Genomics. 2023 Nov 15;16(1):287. doi: 10.1186/s12920-023-01722-5.
As the most common type of glaucoma, the etiology of primary open-angle glaucoma (POAG) has not been unified. Autophagy may affect the occurrence and development of POAG, while the specific mechanism and target need to be further explored.
The GSE27276 dataset from the Gene Expression Omnibus (GEO) database and the autophagy gene set from the GeneCards database were selected to screen differentially expressed autophagy-related genes (DEARGs) of POAG. Hub DEARGs were selected by constructing protein-protein interaction (PPI) networks and utilizing GSE138125 dataset. Subsequently, immune cell infiltration analysis, genome-wide association study (GWAS) analysis, gene set enrichment analysis (GSEA) and other analyses were performed on the hub genes. Eventually, animal experiments were performed to verify the mRNA levels of the hub genes by quantitative real time polymerase chain reaction (qRT-PCR).
A total of 67 DEARGs and 2 hub DEARGs, HSPA8 and RPL15, were selected. The hub genes were closely related to the level of immune cell infiltration. GWAS analysis confirmed that the causative regions of the 2 hub genes in glaucoma were on chromosome 11 and chromosome 3, respectively. GSEA illustrated that pathways enriched for highly expressed HSPA8 and RPL15 contained immunity, autophagy, gene expression and energy metabolism-related pathways. qRT-PCR confirmed that the expression of Hspa8 and Rpl15 in the rat POAG model was consistent with the results of bioinformatics analysis.
This study indicated that HSPA8 and RPL15 may affect the progression of POAG by regulating autophagy and provided new ideas for the pathogenesis and treatment of POAG.
原发性开角型青光眼（POAG）作为最常见的青光眼类型，其病因尚未统一。自噬可能影响 POAG 的发生和发展，但其具体机制和靶点仍需进一步探索。
从基因表达综合数据库（GEO）中选择 GSE27276 数据集和基因卡片数据库中的自噬基因集，筛选 POAG 的差异表达自噬相关基因（DEARGs）。通过构建蛋白质-蛋白质相互作用（PPI）网络，并利用 GSE138125 数据集，选择核心 DEARGs。随后对核心基因进行免疫细胞浸润分析、全基因组关联研究（GWAS）分析、基因集富集分析（GSEA）等分析。最后，通过定量实时聚合酶链反应（qRT-PCR）实验验证核心基因的 mRNA 水平。
共筛选出 67 个 DEARGs 和 2 个核心 DEARGs，HSPA8 和 RPL15。核心基因与免疫细胞浸润水平密切相关。GWAS 分析证实，2 个核心基因在青光眼的致病区域分别位于 11 号染色体和 3 号染色体上。GSEA 表明，高表达 HSPA8 和 RPL15 所富集的途径包含免疫、自噬、基因表达和能量代谢相关途径。qRT-PCR 实验验证了大鼠 POAG 模型中 Hspa8 和 Rpl15 的表达与生物信息学分析结果一致。
本研究表明 HSPA8 和 RPL15 可能通过调节自噬影响 POAG 的进展，为 POAG 的发病机制和治疗提供了新的思路。
