Metabolomics in Age-Related Macular Degeneration: A Systematic Review

Abstract

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.

Metabolomics in Retinal Diseases: An Update

“…Recently, studies of AMD based on metabolomics have significantly increased and have been summarized by both Kersten et al [35] and Hou et al [36]. Here, we expand and summarize metabolomics-based research regarding the association between metabolites and AMD, pathological mechanisms underlying AMD, diagnosis, therapeutic monitoring, and new treatment targets of AMD.…”

“…This pathway has been involved in extensive cellular translation events and cellular energy requirements [158]. Some changes in the concentration of amino acids may result in this bias, which is usually identified by MetaboAnalyst algorithm [36].…”

Proline metabolism and transport in retinal health and disease

“…In aging mice, plasma proline levels are reduced (Seo et al 2016). Multiple metabolomics studies identified significant changes in proline in AMD patients (Hou et al 2020) (Table 2). A recent targeted-metabolomics study also found proline to be one of six significantly changed metabolites among the 188 metabolites analyzed in the plasma of AMD patients (Chao de la Barca et al 2020).…”

Release of Iron-Loaded Ferritin in Sodium Iodate-Induced Model of Age Related Macular Degeneration: An In-Vitro and In-Vivo Study

“…Dysfunction of the retinal pigment epithelial (RPE) cell layer is a consistent observation and is clinically identified with the accumulation of extracellular amorphous material, known as drusen, between the RPE cell layer and inner layer of the Bruch’s membrane. Accumulation of phagocytosed material including break-down products of photoreceptor outer segments (POS) results in the loss of metabolic support and eventual death of RPE and photoreceptor cells, resulting in irreversible vision loss [ 3 , 4 , 5 , 6 , 7 , 8 ].…”