Aqueous humor metabolite profile of pseudoexfoliation glaucoma is distinctive

Myer, Ciara; Abdelrahman, Leila; Banerjee, Santanu; Khattri, Ram B.; Merritt, Matthew E.; Junk, Anna K.; Lee, Richard K.; Bhattacharya, Sanjoy K.

doi:10.1039/c9mo00192a

Cited by 32 publications

(46 citation statements)

References 59 publications

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“…Eighteen studies were identified on the basis of the inclusion and exclusion criteria. 17,18,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] The flow chart for selection of the studies included in this review is shown in Figure 1. All the studies were designed as case-control studies with the sample sizes ranging from 19 to 506.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…Among the 18 studies, 13 focused on open-angle glaucoma (OAG), 17,[20][21][22][23][24][25][26][27][28][29][30][31] two treated any glaucoma as cases, 18,35 and the other three investigated primary angle-closure glaucoma (PACG), primary congenital glaucoma (PCG), and pseudoexfoliation glaucoma, respectively. [32][33][34] Among the 13 studies on OAG, four were performed with aqueous humor (AH) samples, [20][21][22][23] three with serum samples, [24][25][26] three with plasma samples, 17,27,28 and the other three with tear samples, 29 occipital brain region, 30 and optic nerve, 31 respectively. Characteristics of the studies are summarized in Table 1.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

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Metabolomics in Glaucoma: A Systematic Review

Wang

Hou

Liang

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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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.

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Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Metabolomics in Glaucoma: A Systematic Review

Wang

Hou

Liang

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 50%

“…To the best of our knowledge, only one metabolomics study of AH from patients with pseudoexfoliation glaucoma, not XFS, has been conducted thus far (Myer et al, 2020). Similarly to Myer et al (2020), we have found decreased levels of L-arginine. Interestingly, according to Leruez et al neither arginine nor tryptophan proved to be significant in the plasma of XFS (Leruez et al, 2018), which implies that the metabolism of these amino acids in XFS is affected locally, in the anterior chamber of the eye, rather than systemically.…”

Section: Discussionmentioning

confidence: 50%

“…This is the first study on the metabolomics of AH in XFS. To the best of our knowledge, the metabolomics of AH was the subject of only one published study involving patients with pseudoexfoliation glaucoma (Myer et al, 2020). Moreover, some authors analyzed the proteomics of AH in pseudoexfoliation glaucoma (Kliuchnikova et al, 2016;Sharma et al, 2018;Botling Taube et al, 2019) and plasma metabolomics in XFS (Leruez et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Metabolomics Reveals Differences in Aqueous Humor Composition in Patients With and Without Pseudoexfoliation Syndrome

Dmuchowska

Pietrowska

Krasnicki

et al. 2021

Front. Mol. Biosci.

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Pseudoexfoliation syndrome (XFS) is stress- or inflammation-induced elastosis accompanied by excessive production of microfibrils and their deposition in the anterior segment of the eye. Approximately 60–70 million people are affected by XFS worldwide. It is a component of a systemic disorder, considered a major risk factor for accelerated cataract formation, cataract surgery complications and development of glaucoma, which untreated or inadequately treated may lead to blindness. Moreover, XFS has been associated with cardiovascular and cerebrovascular morbidity, dementia, sensorineural hearing loss and pelvic organ prolapse. The pathogenesis of XFS has not been fully elucidated yet. Aqueous humor (AH) is a transparent fluid filling the anterior and posterior chambers of the eye. Determination of AH metabolites that are characteristic for XFS may provide valuable information about the molecular background of this ocular disorder. The aim of this study was to compare the composition of AH in XFS and non-XFS patients undergoing cataract surgery. The AH samples from 34 patients (15 with XFS and 19 without) were analyzed using liquid chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (LC-QTOF-MS). The obtained metabolic fingerprints were analyzed using multivariate statistics. Eleven statistically significant metabolites were identified. Compared with the non-XFS group, the AH of patients with XFS contained significantly lower levels of amino acids and their derivatives, for example, arginine (−31%, VIP = 2.38) and homo-arginine (−19%, VIP = 1.38). Also, a decrease in the levels of two acylcarnitines, hydroxybutyrylcarnitine (−29%, VIP = 1.24) and decatrienoylcarnitine (−46%, VIP = 1.89), was observed. However, the level of indoleacetaldehyde in XFS patients was significantly higher (+96%, VIP = 2.64). Other significant metabolites were two well-recognized antioxidants, ascorbic acid (−33%, VIP = 2.11) and hydroxyanthranilic acid (−33%, VIP = 2.25), as well as S-adenosylmethionine, a compound with anti-inflammatory properties (−29%, VIP = 1.93). Metabolic pathway analysis demonstrated that the identified metabolites belonged to eight metabolic pathways, with cysteine and methionine metabolism as well as arginine and proline metabolism being the most frequently represented. XFS can be associated with enhanced oxidative stress and inflammation, as well as with the disturbances of cellular respiration and mitochondrial energy production. Implementation of non-targeted metabolomics provided a better insight into the still not fully understood pathogenesis of XFS.

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Magnetic resonance quantification of skeletal muscle lipid infiltration in a humanized mouse model of Duchenne muscular dystrophy

et al. 2022

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Rodent models of Duchenne muscular dystrophy (DMD) often do not recapitulate the severity of muscle wasting and resultant fibro‐fatty infiltration observed in DMD patients. Having recently documented severe muscle wasting and fatty deposition in two preclinical models of muscular dystrophy (Dysferlin‐null and mdx mice) through apolipoprotein E (ApoE) gene deletion without and with cholesterol‐, triglyceride‐rich Western diet supplementation, we sought to determine whether magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) could be used to detect, characterize, and compare lipid deposition in mdx‐ApoE knockout with mdx mice in a diet‐dependent manner. MRI revealed that both mdx and mdx‐ApoE mice exhibited elevated proton relaxation time constants (T2) in their lower hindlimbs irrespective of diet, indicating both chronic muscle damage and fatty tissue deposition. The mdx‐ApoE mice on a Western diet (mdx‐ApoEW) presented with greatest fatty tissue infiltration in the posterior compartment of the hindlimb compared with other groups, as detected by MRI/MRS. High‐resolution magic angle spinning confirmed elevated lipid deposition in the posterior compartments of mdx‐ApoEW mice in vivo and ex vivo, respectively. In conclusion, the mdx‐ApoEW model recapitulates some of the extreme fatty tissue deposition observed clinically in DMD muscle but typically absent in mdx mice. This preclinical model will help facilitate the development of new imaging modalities directly relevant to the image contrast generated in DMD, and help to refine MR‐based biomarkers and their relationship to tissue structure and disease progression.

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Aqueous humor metabolite profile of pseudoexfoliation glaucoma is distinctive

Abstract: We identified 298 metabolites in pseudoexfoliation (PEX) glaucoma, primary open angle glaucoma (POAG) and non-glaucomatous controls. Machine learning can classify aqueous humor into the three distinct categories and presents the opportunity for future predictions.

Cited by 32 publications

References 59 publications

Metabolomics in Glaucoma: A Systematic Review

Metabolomics in Glaucoma: A Systematic Review

Metabolomics Reveals Differences in Aqueous Humor Composition in Patients With and Without Pseudoexfoliation Syndrome

Magnetic resonance quantification of skeletal muscle lipid infiltration in a humanized mouse model of Duchenne muscular dystrophy

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