Metabolomics in Glaucoma: A Systematic Review

Abstract

PURPOSE. Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and blindness. The aim of this review is to provide current metabolic profiles for glaucoma through a summary and analysis of reported metabolites associated with glaucoma. METHODS.We searched PubMed and Web of Science for metabolomics studies of humans on glaucoma published before November 11, 2020. Studies were included if they assessed the biomarkers of any types of glaucoma and performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach. Pathway enrichment analysis and topology analysis were performed to generate a global view of metabolic signatures related to glaucoma using the MetaboAnalyst 3.0. RESULTS.In total, 18 articles were included in this review, among which 13 studies were focused on open-angle glaucoma (OAG). Seventeen metabolites related to OAG were repeatedly identified, including seven amino acids (arginine, glycine, alanine, lysine, methionine, phenylalanine, tyrosine), two phosphatidylcholine (PC aa C34:2, PC aa C36:4), three complements (acetylcarnitine, propionylcarnitine, butyrylcarnitine), carnitine, glutamine, hypoxanthine, spermine, and spermidine. The pathway analysis implied a major role of amino metabolism in OAG pathophysiology and revealed the metabolic characteristics between different biological samples. CONCLUSIONS.In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma. Additional studies are needed to validate existing findings, and future research will need to explore the potential overlap between different biological fluids.

Plasma metabolomics of primary open-angle glaucoma in three prospective US cohorts and the UK Biobank

“…Of note, the systematic review identified 12 metabolites that have been identified across the various metabolomics studies as being associated with open-angle glaucoma in at least 2 studies; of these, two were phospholipids (PCs), 2 were organic acids and derivatives (including amino acids), and 2 were carnitines. 9 Our results are consistent with prior studies in identifying phospholipids and various organic acids and derivatives in both the NHS/NHS2/HPFS and UK Biobank, while also showing support for the role of lipids, particularly diglycerides, triglycerides and other lipids (e.g., cholesteryl esters).…”

“…However, LPCs are proinflammatory and pro-oxidant, 53 and they may play a role in the autotaxin-lysophophatidic acid pathway in intraocular pressure regulation. 35,37,[54][55][56][57] Our results are consistent with other targeted lipidomic studies of glaucoma that have revealed higher specific phospholipids in blood, 9 the trabecular meshwork or aqueous humor of glaucomatous eyes. 55,56,58,59 Mitochondrial dysfunction, carnitines and organic acids and derivatives Mitochondrial dysfunction has been hypothesized as a key component of POAG pathophysiology.…”

“…A systematic review 9 has identified 13 studies to date on the metabolomics of open-angle glaucoma. Of these, 3 evaluated serum, 29–31 and 3 evaluated plasma 32–34 while others have evaluated aqueous humor, 35–38 tear 39 and optic nerve 40 samples; these studies have collectively assessed ~140 different metabolites.…”

“…Metabolomics platforms quantify blood metabolites and can be used to evaluate the etiologic role of metabolic alterations. Multiple proteomic and metabolomics studies of prevalent POAG/glaucoma have been conducted, [5][6][7][8][9] and some novel markers have been found to be associated with POAG. However, this approach may be problematic for the discovery of changes related to early disease, as consequences of advanced disease or treatment are likely to impact circulating metabolite profiles with the use of prevalent glaucoma cases.…”

Metabolomics in Retinal Diseases: An Update

“…There are several reviews concerning the application of metabolomics in glaucoma [113,114] and studies of glaucoma based on a metabolomics approach. We retrieved 16 full-text articles in the area of clinical metabolomics from the PubMed database (Table 4).…”