Purpose Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly, and the exact pathogenesis of the AMD remains unclear. The purpose of this review is to summarize potential metabolic biomarkers and pathways of AMD that might facilitate risk predictions and clinical diagnoses of AMD. Methods We obtained relevant publications of metabolomics studies of human beings by systematically searching the MEDLINE (PubMed) database before June 2020. Studies were included if they performed mass spectrometry–based or nuclear magnetic resonance–based metabolomics approach for humans. In addition, AMD was assessed from fundus photographs based on standardized protocols. The metabolic pathway analysis was performed using MetaboAnalyst 3.0. Results Thirteen studies were included in this review. Repeatedly identified metabolites including phenylalanine, adenosine, hypoxanthine, tyrosine, creatine, citrate, carnitine, proline, and maltose have the possibility of being biomarkers of AMD. Validation of the biomarker panels was observed in one study. Dysregulation of metabolic pathways involves lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, and translation, which might play important roles in the development and progression of AMD. Conclusions This review summarizes the potential metabolic biomarkers and pathways related to AMD, providing opportunities for the construction of diagnostic or predictive models for AMD and the discovery of new therapeutic targets.

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.

PURPOSE. Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures. METHODS.We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database. RESULTS.We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including L-glutamine, L-lactic acid, pyruvic acid, acetic acid, L-glutamic acid, D-glucose, L-alanine, L-threonine, citrulline, L-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that L-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism. CONCLUSIONS.This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.

No abstract

The retina is one of the most important structures in the eye, and the vascular health of the retina and choroid is critical to visual function. Metabolomics provides an analytical approach to endogenous small molecule metabolites in organisms, summarizes the results of “gene-environment interactions”, and is an ideal analytical tool to obtain “biomarkers” related to disease information. This study discusses the metabolic changes in neovascular diseases involving the retina and discusses the progress of the study from the perspective of metabolomics design and analysis. This study advocates a comparative strategy based on existing studies, which encompasses optimization of the performance of newly identified biomarkers and the consideration of the basis of existing studies, which facilitates quality control of newly discovered biomarkers and is recommended as an additional reference strategy for new biomarker discovery. Finally, by describing the metabolic mechanisms of retinal and choroidal neovascularization, based on the results of existing studies, this study provides potential opportunities to find new therapeutic approaches.