Golpour Navid, Brautaset Rune L, Hui Flora, Nilsson Maria, Svensson Jonas E, Williams Pete A, Tribble James R
Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
BMJ Open Ophthalmol. 2025 Mar 13;10(1):e002103. doi: 10.1136/bmjophth-2024-002103.
Glaucoma, a leading cause of irreversible blindness worldwide, is characterised by retinal ganglion cell degeneration. Increasing evidence points to metabolic dysfunction, particularly mitochondrial dysfunction, as a contributing factor to glaucomatous neurodegeneration. This systematic review and meta-analysis aimed to identify key metabolic pathways and biomarkers associated with primary open-angle glaucoma (POAG).
A systematic literature search was conducted to identify studies measuring metabolites in plasma and aqueous humour from patients with POAG using metabolomics techniques. Enrichment analyses for significantly increased metabolites were conducted using MetaboAnalyst. Meta-analyses were performed using random-effects models to calculate effect sizes for metabolites reported in at least three studies.
17 studies involving patients with POAG were included. Pathway analysis revealed significant enrichment of the arginine and proline metabolism pathway in both aqueous humour and plasma. Additionally, the phenylalanine metabolism pathway was enriched in plasma. These pathways are associated with oxidative stress and neurodegeneration, both of which are key factors in POAG pathology. Meta-analysis identified several significantly elevated metabolites, including lysine, glutamine, alanine, histidine, carnitine and creatinine in aqueous humour, as well as methionine in plasma.
This study underscores the central role of metabolic dysfunction in POAG, highlighting specific metabolites and pathways that could serve as biomarkers for early diagnosis and therapeutic intervention. Future research should prioritise longitudinal studies and untargeted metabolomic profiling to further deepen our understanding of metabolic changes and their contributions to glaucoma progression.
CRD42024512098.
青光眼是全球不可逆性失明的主要原因，其特征为视网膜神经节细胞变性。越来越多的证据表明，代谢功能障碍，尤其是线粒体功能障碍，是青光眼性神经变性的一个促成因素。本系统评价和荟萃分析旨在确定与原发性开角型青光眼（POAG）相关的关键代谢途径和生物标志物。
进行系统的文献检索，以确定使用代谢组学技术测量POAG患者血浆和房水中代谢物的研究。使用MetaboAnalyst对显著增加的代谢物进行富集分析。采用随机效应模型进行荟萃分析，以计算至少三项研究中报告的代谢物的效应量。
纳入了17项涉及POAG患者的研究。通路分析显示，房水和血浆中精氨酸和脯氨酸代谢途径均有显著富集。此外，血浆中苯丙氨酸代谢途径也有富集。这些途径与氧化应激和神经变性有关，而氧化应激和神经变性都是POAG病理的关键因素。荟萃分析确定了几种显著升高的代谢物，包括房水中的赖氨酸、谷氨酰胺、丙氨酸、组氨酸、肉碱和肌酐，以及血浆中的蛋氨酸。
本研究强调了代谢功能障碍在POAG中的核心作用，突出了特定的代谢物和途径，这些代谢物和途径可作为早期诊断和治疗干预的生物标志物。未来的研究应优先进行纵向研究和非靶向代谢组学分析，以进一步加深我们对代谢变化及其对青光眼进展的贡献的理解。
PROSPERO注册号：CRD42024512098。
