Primary open-angle glaucoma (POAG) is a genetically, physiologically, and phenotypically complex neurodegenerative disorder. This study addressed the expanding collection of genes associated with POAG, referred to as the “POAGome.” We used bioinformatics tools to perform an extensive, systematic literature search and compiled 542 genes with confirmed associations with POAG and its related phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, and primary congenital glaucoma). The genes were classified according to their associated ocular tissues and phenotypes, and functional annotation and pathway analyses were subsequently performed. Our study reveals that no single molecular pathway can encompass the pathophysiology of POAG. The analyses suggested that inflammation and senescence may play pivotal roles in both the development and perpetuation of the retinal ganglion cell degeneration seen in POAG. The TGF-β signaling pathway was repeatedly implicated in our analyses, suggesting that it may be an important contributor to the manifestation of POAG in the anterior and posterior segments of the globe. We propose a molecular model of POAG revolving around TGF-β signaling, which incorporates the roles of inflammation and senescence in this disease. Finally, we highlight emerging molecular therapies that show promise for treating POAG.

原发性开角型青光眼 (POAG) 是一种遗传、生理和表型复杂的神经退行性疾病。这项研究涉及与 POAG 相关的不断扩大的基因集合，称为“POAGome”。我们使用生物信息学工具进行了广泛、系统的文献检索，并编译了 542 个已证实与 POAG 及其相关表型（正常眼压性青光眼、高眼压症、青少年开角型青光眼和原发性先天性青光眼）相关的基因。根据相关的眼组织和表型对基因进行分类，随后进行功能注释和通路分析。我们的研究表明，没有任何单一分子途径可以涵盖 POAG 的病理生理学。分析表明，炎症和衰老可能在 POAG 中视网膜神经节细胞变性的发生和延续中发挥关键作用。 TGF-β信号通路在我们的分析中反复出现，表明它可能是眼球前段和后段 POAG 表现的重要贡献者。我们提出了一种围绕 TGF-β 信号传导的 POAG 分子模型，其中结合了炎症和衰老在这种疾病中的作用。最后，我们重点介绍有望治疗 POAG 的新兴分子疗法。