Progress toward personalized medicine for glaucoma

Moroi, Sayoko E.; Raoof, Duna; Reed, David; Zöllner, Sebastian; Qin, Zhaohui S.; Richards, Julia E.

doi:10.1586/eop.09.6

Cited by 14 publications

(9 citation statements)

References 92 publications

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“…The incidence differs considerably between races, and the clinical manifestation and progression profiles are variable [11] . Genetic mutations and common genetic variants have been linked to several types of glaucoma, but these factors can only explain a small portion of all cases [45] .…”

Section: Metabolomics In Glaucomamentioning

confidence: 99%

Clinical Metabolomics and Glaucoma

Breda

Himmelreich²,

Ghesquière³

et al. 2017

Ophthalmic Res

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Glaucoma is one of the leading causes of irreversible blindness worldwide. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression. Metabolomics is the study of all metabolites in an organism, and it has the potential to provide a biomarker. This review summarizes the findings of metabolomics in glaucoma patients and explains why this field is promising for new research. We identified published studies that focused on metabolomics and ophthalmology. After providing an overview of metabolomics in ophthalmology, we focused on human glaucoma studies. Five studies have been conducted in glaucoma patients and all compared patients to healthy controls. Using mass spectrometry, significant differences were found in blood plasma in the metabolic pathways that involve palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors. For nuclear magnetic resonance spectroscopy, a high glutamine-glutamate/creatine ratio was found in the vitreous and lateral geniculate body; no differences were detected in the optic radiations, and a lower N-acetylaspartate/choline ratio was observed in the geniculocalcarine and striate areas. Metabolomics can move glaucoma care towards a personalized approach and provide new knowledge concerning the pathophysiology of glaucoma, which can lead to new therapeutic options.

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Section: Metabolomics In Glaucomamentioning

confidence: 99%

Clinical Metabolomics and Glaucoma

Breda

Himmelreich²,

Ghesquière³

et al. 2017

Ophthalmic Res

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“…It is characterized by a progressive optic neuropathy arising from apoptotic cell death of retinal ganglion cells (Nickells 2012). Genetic causes for several Mendelian forms of glaucoma have been reported [reviewed in Moroi et al (2009) and Wiggs (2012)], but these genes do not play a major role in the common age-related forms of POAG. Recently, genome-wide association studies (GWAS) for POAG have successfully identified common variants near CAV1 and CAV2 in an Icelandic cohort (Thorleifsson et al 2010), in TMCO1 and CDKN2B - AS1 in an Australian cohort (Burdon et al 2011), and in CDKN2B-AS and SIX1/SIX6 regions in individuals of European ancestry (Wiggs et al 2012b).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study and meta-analysis of intraocular pressure

et al. 2013

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Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10−8). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.

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“…1 The high variation of incidence among races 2 and the variation in clinical manifestations of glaucoma 3 emphasize the need to understand how specific genetic and/or metabolic differences among individuals significantly influence disease status. The risk of glaucoma is increased by multiple genetic factors susceptible to the influence of numerous environmental exposures.…”

mentioning

confidence: 99%

Metabolome-Wide Association Study of Primary Open Angle Glaucoma

Burgess

Uppal

Walker

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics. METHODS.We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG.RESULTS. Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR ¼ 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways.CONCLUSIONS. Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods.

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Progress toward personalized medicine for glaucoma

Cited by 14 publications

References 92 publications

Clinical Metabolomics and Glaucoma

Clinical Metabolomics and Glaucoma

Genome-wide association study and meta-analysis of intraocular pressure

Metabolome-Wide Association Study of Primary Open Angle Glaucoma

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