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

Liu, Aihua; Wang, Liming; Feng, Qiang; Zhang, Dandan; Ke-xi, Chen; Yiming, Guli Humaer; Wang, Qiong; Hong, Yaru; Whelchel, Amy; Zhang, Xiaomin; Li, Xiaorong; Dong, Lijie

doi:10.1111/jcmm.16361

Cited by 14 publications

(12 citation statements)

References 51 publications

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

Tonner¹,

Hunn²,

Auler³

et al. 2022

IJMS

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Slow and progressive loss of retinal ganglion cells (RGCs) is the main characteristic of glaucoma, the second leading cause of blindness worldwide. Previous studies have shown that impaired mitochondrial dynamics could facilitate retinal neurodegeneration. Mitochondrial dynamics are regulated directly (fission) or more indirectly (fusion) by dynamin-like protein 1 (DNML1). Therefore, DNM1L might be a promising target for an antibody-based approach to treat glaucoma. The consequences of targeting endogenous DNM1L by antibodies in a glaucoma animal model have not been investigated yet. Here, we show that the intravitreal application of an anti-DNM1L antibody showed protective effects regarding the survival of RGCs and their axons in the retinal nerve fiber layer (RNFL). Antibody treatment also improved retinal functionality, as observed by electroretinography (Ganzfeld ERG). Western blot analysis revealed altered DNM1L phosphorylation and altered expression of proteins related to apoptosis suggesting a decreased apoptosis rate. Mass spectrometry analysis revealed 28 up-regulated and 21 down-regulated proteins (p < 0.05) in both experimental groups. Protein pathway analysis showed that many proteins interacted directly with the target protein DNM1L and could be classified into three main protein clusters: Vesicle traffic-associated (NSF, SNCA, ARF1), mitochondrion-associated (HSP9A, SLC25A5/ANT2, GLUD1) and cytoskeleton-associated (MAP1A) signaling pathway. Our results demonstrate that DNM1L is a promising target for an antibody-based approach to glaucoma therapy.

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Section: Discussionmentioning

confidence: 99%

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

Tonner¹,

Hunn²,

Auler³

et al. 2022

IJMS

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“…The method of proteolysis was based on sodium dodecyl sulphate polyacrylamide gel electrophoresis as performed previously 26 . The SDS‐PAGE was performed with 5 μg of protein per sample; the gel was stained and then destained until the background was clear.…”

Section: Methodsmentioning

confidence: 99%

“…20 The application of this technology to different diseases has improved our understanding of disease mechanisms [21][22][23] and highlighted new disease biomarkers and therapeutic methods. [24][25][26] In this study, we initially hypothesized that angle closure is related to AH change in primary angle-closure glaucoma (PACG) and some proteins in AH could reflect the anterior chamber angle before neuropathy. The aim of this study was to analyse the characteristics of differentially expressed proteins (DEPs) based on the AH proteomes of APAC patients and to discover valuable information for treatment in the early stage of PACG.…”

Section: Introductionmentioning

confidence: 99%

“…Mass spectrometry‐based proteomic and bioinformatic methods have enabled the comparison of proteins in a variety of biological samples with a high level of resolution and accuracy 20 . The application of this technology to different diseases has improved our understanding of disease mechanisms 21–23 and highlighted new disease biomarkers and therapeutic methods 24–26 …”

Section: Introductionmentioning

confidence: 99%

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Low expression of TGF‐β2 and matrilin2 in human aqueous humour with acute primary angle closure

Wang,

Xu,

Hong

et al. 2024

J Cellular Molecular Medi

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Primary angle‐closure glaucoma (PACG) is the leading cause of irreversible blindness in the world. Angle closure induced by pupil block and secondary iris synechia is the fundamental pathology of the PACG. The molecular mechanisms of angle closure have not yet been clearly illustrated. This study was designed to investigate the protein difference in the aqueous humour and explore new biomarker of the PACG. Aqueous humour (AH) was collected from patients with acute primary angle closure (APAC) and cataract (n = 10 in APAC group) and patients with cataract only (n = 10 in control group). Samples were pooled and measured using label‐free proteome technology. Then, the differentially expressed proteins (DEPs) were verified by ELISA using independent AH samples (n = 20 each group). More than 400 proteins were revealed in both groups through proteomics. Comparing the two groups, there were 91DEPs. These proteins participate in biological activities such as inflammation, fibrosis, nerve growth and degeneration and metabolism. We found that the expression of transforming growth factor‐β2 and matrilin2 was downregulated in the APAC group. The two proteins are related to inflammation and extracellular matrix formation, which might be involved in angle closure. This study characterized DEPs in AH of the APAC and found a downregulated protein matrilin2.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Idiopathic epiretinal membrane (iERM) is a pathological fibrocellular change in the vitreoretinal junction over the macular area; however, possible pathogenic mechanisms remain unclear. Changes in the differential protein composition of the aqueous humor (AH) may represent potential molecular changes associated with iERM. To gain new insights into the molecular mechanisms of iERM pathology, a sensitive label-free proteomics analysis was performed to compare AH protein expressions in patients with cataracts with or without iERM. This study employed nanoflow ultra-high-performance liquid chromatography-tandem mass spectrometry to investigate protein compositions of the AH obtained from individual human cataract eyes from 10 patients with iERM and 10 age-matched controls without iERM. Eight proteins were differentially expressed between the iERM and control samples, among which six proteins were upregulated and two were downregulated. A gene ontology (GO) analysis revealed that iERM was closely associated with several biological processes, such as immunity interactions, cell proliferation, and extracellular matrix remodeling. Additionally, multiple proteins, including lumican, cyclin-dependent kinase 13, and collagen alpha-3(VI) chain, were correlated with the central retinal thickness, indicating a multifactorial response in the pathogenic process of iERM. Changes in the AH level of lumican between iERM and control samples were also confirmed by an enzyme-linked immunosorbent assay. In conclusion, several pathological pathways involved in iERM were identified in the AH by a proteomic analysis, including immune reactions, cell proliferation, and remodeling of the extracellular matrix. Lumican is a potential aqueous biomarker for predicting iERM development and monitoring its progression. More clinical parameters also need to be identified to complete the analysis, and those could provide additional targets for treating and preventing iERM.

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

Cited by 14 publications

References 51 publications

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

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

Low expression of TGF‐β2 and matrilin2 in human aqueous humour with acute primary angle closure

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

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