Low expression of GSTP1 in the aqueous humour of patients with primary open‐angle glaucoma

Abstract

Primary open‐angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high‐resolution, label‐free, liquid chromatography‐tandem mass spectrometry‐based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up‐regulated proteins and 49 down‐regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle‐mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down‐regulated expression of glutathione S‐transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme‐linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox‐related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.

The role of artificial intelligence in analysis of biofluid markers for diagnosis and management of glaucoma: A systematic review

“…34,47,58 Only nine total biomarkers were noted to be significantly different in glaucoma patients across two or more studies. 8,9,25,27,28,34,36,41,42,[44][45][46][47][48][49][51][52][53]55,[58][59][60][61]63,64 Further, as there was minimal reporting of non-significant biomarkers, it is likely that the variability in findings is even greater than reported in the literature. With no strong, replicable, characteristic biomarkers for each glaucoma subtype, the biomarkers provide little insight in glaucoma etiology.…”

“…While many studies looked at entire metabolomic or proteomic profiles to determine changes in POAG, there was heterogeneity in the data with reporting of over 175 unique, differentially expressed biomarkers, over 75 biological pathways implicated in POAG development, and over 50 unique biomarkers determined to be non-significant. 8,9,25,27,28,33,34,36,[41][42][43][44][45][46][47][48][49][51][52][53]55,[58][59][60][61]63,64 Studies each identified between one and 773 differentially expressed biomarkers. Many studies using unsupervised AI to look for differentially expressed markers did not report all non-significant biomarkers investigated.…”

“…34,47,58 Pathways implicated in POAG by multiple studies included the glycolytic pathway, inflammation, autoimmune mechanisms, extracellular matrix-receptor interaction, cellular transport, cell-cell signalling, and signal transduction. 27,28,41,42,51,63 The glycolytic, inflammatory, and autoimmune pathways were the most commonly implicated, each referenced by three studies. 27,28,41,42,51 Despite the lack of similar findings between studies, various diagnostic and prognostic predictive AI models were developed using identified biomarkers.…”

Dynamin-like Protein 1 (DNML1) as a Molecular Target for Antibody-Based Immunotherapy to Treat Glaucoma

“…COTL1 overexpression showed disturbed neuronal morphology and exhibited AD-like neuropathology [ 82 , 83 ]. In a study with POAG patients, COTL1 was up-regulated in aqueous humor [ 84 ]. Therefore, the low abundance of COTL1 suggested continued polymerization and stabilization of the actin cytoskeleton, which, together with MT cytoskeleton stabilization, may be part of a neuroprotective mechanism, as shown in previous studies [ 26 , 85 ].…”

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

“…The emergence of liquid biopsies for diabetic retinopathies and other vitreoretinal diseases was also noted for precision medicine [13,14]. Recent proteomics studies of human AH revealed many proteins in patients with intraocular disease [13,[15][16][17][18][19]. Pollreisz et al [20] first performed isobaric tags for relative and absolute quantitation (iTRAQ) 4-plex quantitative protein analysis of the aqueous and vitreous fluids from human eyes with iERM.…”