Du Rong, Kumar Ajay, Yang Enzhi, Zhang Jingxue, Wang Ningli, Du Yiqin
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Key Laboratory of Intelligent Diagnosis Technology and Equipment for Optic Nerve-Related Eye Diseases, Capital Medical University, Beijing 100730, China.
Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Curr Issues Mol Biol. 2025 Jul 3;47(7):514. doi: 10.3390/cimb47070514.
Glaucoma is a leading cause of irreversible blindness, normally associated with dysfunction and degeneration of the trabecular meshwork (TM) as the primary cause. Trabecular meshwork stem cells (TMSCs) have emerged as promising candidates for TM regeneration toward glaucoma therapies, yet their molecular characteristics remain poorly defined. In this study, we performed a comprehensive transcriptomic comparison of human TMSCs and human TM cells (TMCs) using RNA sequencing and microarray analyses, followed by qPCR validation. A total of 465 differentially expressed genes were identified, with 254 upregulated in TMSCs and 211 in TMCs. A functional enrichment analysis revealed that TMSCs are associated with development, immune signaling, and extracellular matrix remodeling pathways, while TMCs are enriched in structural, contractile, and adhesion-related functions. A network topology analysis identified , , and as robust TMSC-specific hub genes, and and as TMC-specific markers, with expression patterns confirmed by qPCR. These findings define distinct molecular signatures of TMSCs and TMCs, providing reliable biomarkers for cell identity and a foundation for future stem cell-based therapies targeting TM dysfunction in glaucoma.
青光眼是不可逆性失明的主要原因，通常与小梁网（TM）功能障碍和变性作为主要病因相关。小梁网干细胞（TMSCs）已成为用于青光眼治疗的小梁网再生的有前景的候选细胞，但其分子特征仍不清楚。在本研究中，我们使用RNA测序和微阵列分析对人TMSCs和人小梁网细胞（TMCs）进行了全面的转录组比较，随后进行了qPCR验证。共鉴定出465个差异表达基因，其中254个在TMSCs中上调，211个在TMCs中上调。功能富集分析表明，TMSCs与发育、免疫信号传导和细胞外基质重塑途径相关，而TMCs则富集于结构、收缩和粘附相关功能。网络拓扑分析确定 、 和 为强大的TMSC特异性枢纽基因， 和 为TMC特异性标志物，其表达模式经qPCR证实。这些发现定义了TMSCs和TMCs不同的分子特征，为细胞身份提供了可靠的生物标志物，并为未来针对青光眼小梁网功能障碍的基于干细胞的治疗奠定了基础。
