Differentiation of soluble aqueous humor metabolites in primary open angle glaucoma and controls

Myer, Ciara; Perez, Jordan; Abdelrahman, Leila; Méndez, Roberto; Khattri, Ram B.; Junk, Anna K.; Bhattacharya, Sanjoy K.

doi:10.1016/j.exer.2020.108024

Cited by 34 publications

(47 citation statements)

References 34 publications

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“…The AH composition changes depending on the metabolites produced during its generation and those acquired from different anterior segment regions during its passage. Several factors may contribute to modifying these metabolites, including the time of collection, severity of the disease, body temperature and IOP fluctuations [ 89 ]. However, a constant pattern is emerging from AH analysis of glaucomatous patients in terms of significant differences in protein profiles and antioxidant defence content [ 90 ].…”

Section: Oxidative Stress and Mitochondria Dysfunctionmentioning

confidence: 99%

Neuroinflammation in Primary Open-Angle Glaucoma

Vernazza

Tirendi

Bassi

et al. 2020

JCM

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Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increasing evidence suggests oxidative damage and immune response defects are key factors contributing to glaucoma onset. Indeed, both the failure of the trabecular meshwork tissue in the conventional outflow pathway and the neuroinflammation process, which drives the neurodegeneration, seem to be linked to the age-related over-production of free radicals (i.e., mitochondrial dysfunction) and to oxidative stress-linked immunostimulatory signaling. Several previous studies have described a wide range of oxidative stress-related makers which are found in glaucomatous patients, including low levels of antioxidant defences, dysfunction/activation of glial cells, the activation of the NF-κB pathway and the up-regulation of pro-inflammatory cytokines, and so on. However, the intraocular pressure is still currently the only risk factor modifiable by medication or glaucoma surgery. This present review aims to summarize the multiple cellular processes, which promote different risk factors in glaucoma including aging, oxidative stress, trabecular meshwork defects, glial activation response, neurodegenerative insults, and the altered regulation of immune response.

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Section: Oxidative Stress and Mitochondria Dysfunctionmentioning

confidence: 99%

Neuroinflammation in Primary Open-Angle Glaucoma

Vernazza

Tirendi

Bassi

et al. 2020

JCM

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“…To the best of our knowledge, there are only few studies investigating biomarkers in POAG via metabolomic approaches (Edwards et al, 2014;Burgess et al, 2015;Leruez et al, 2018;Buisset et al, 2019;Tang et al, 2019;Kouassi Nzoughet et al, 2020;Myer et al, 2020;Pan et al, 2020). Previous results showed discriminant metabolites involved in steroid biosynthesis, mitochondrial oxidation of energetic substrates, senescence and polyamines function in the plasma of POAG patients (Burgess et al, 2015;Leruez et al, 2018;Kouassi Nzoughet et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy

et al. 2021

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Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3′-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.

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“…AH composition depends on the metabolites produced during its generation and those acquired during its passage through various anterior segment regions [ 68 ]. Since the proteomic AH profile of POAG patients is completely altered compared to healthy individuals [ 59 ], it is significant to investigate a large number of pro-/anti-oxidation agents that are found in the AH of POAG patients exposed to oxidative stress.…”

Section: Ah Composition Alternations As Response To Oxidative Strementioning

confidence: 99%

Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

Tabak

Schreiber‐Avissar

Beit‐Yannai

2021

IJMS

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Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

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Differentiation of soluble aqueous humor metabolites in primary open angle glaucoma and controls

Cited by 34 publications

References 34 publications

Neuroinflammation in Primary Open-Angle Glaucoma

Neuroinflammation in Primary Open-Angle Glaucoma

Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy

Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

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