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Experimental and clinical assessment of angiogenesis-related parameters inpatients with juvenile idiopathic arthritis-associated uveitis

ABSTRACT: Introduction: In chronic and treatment-resistant cases of juvenile idiopathic arthritis-associated uveitis (JIAU), alterations of the iris vasculature may be observed clinically. We sought to investigate this phenomenon by combining clinical and laboratory analyses. Methods: Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n=30) or acute anterior uveitis (AAU; n=18), and primary open angle glaucoma (POAG; n=20) were obtained during ocular surgery. Samples were analyzed by RNA-sequencing (RNA-Seq), qRT-PCR, liquid chromatography, high–definition mass spectrometry technique (LC-MS), Western-Blot (WB), and LEGENDplex analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). Results: RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed significant upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG). LC-MS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which asporin, lumican and decorin were associated with angiogenesis and showed increased (p>0.05) expression on WB analysis. LEGENDplex analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIAU patients with treatment-refractory complicated course of uveitis. Conclusion: Angiogenesis-related genes and proteins are upregulated in the iris tissue of JIAU patients, correlating with increased vascular permeability, hypoperfusion, and neovascularization of the anterior uveal tissue in chronic and complicated JIAU.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171745 | GEO | 2021/04/09

REPOSITORIES: GEO

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Project description:Glaucoma is a group of diseases characterized by progressive optic nerve damage leading to irreversible visual field loss, often associated with elevated intraocular pressure (IOP). However, the specific underlying factors or molecular mechanisms distinguishing various glaucoma subtypes are still not fully understood. In this study, we enrolled a total of 27 subjects, comprising 5 exfoliation syndrome (XFS), 4 exfoliation glaucoma (XFG), 11 primary open-angle glaucoma (POAG), and 7 cataract patients (Control) for a comparative multi-omics analysis including both proteomics and metabolomics of the aqueous humor (AH). The AH proteome and metabolome were analyzed separately using data-independent acquisition (DIA) and data-dependent acquisition (DDA) methods, after which the results were additionally integrated for a comprehensive analysis. The comparative proteomics analysis led to the identification of differentially expressed proteins (DEPs) related to lipid metabolism, complement activation, and extracellular matrix (ECM) regulation, which were commonly up-regulated in both XFG and POAG groups. The metabolomics analysis revealed differentially expressed metabolites (DEMs) particularly those involved in amino acids, suggesting their role in antioxidative processes. Thus, bioinformatic analysis suggested significant substances, such as VTN, APOA1, C6, and L-phenylalanine, that showed quantitative alterations in glaucoma patients. In addition, the integrating the individual omics analyses revealed interaction networks involving PLG, APOA1, and L-phenylalanine, or C3, APOD, and L-valine, suggesting the quantitative relationship in protein-metabolite interactions related to inflammation and lipid metabolism within the AH of glaucoma patients. Furthermore, the correlation approach identified a relationship between FGG and L-phenylalanine, and VTN and inosine, implying potential interactions among compounds not previously identified. These findings would provide valuable insights into the complex molecular mechanism differentiating glaucoma subtypes and may benefit further research into the clinical application of AH proteome and metabolome.

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Experimental and clinical assessment of angiogenesis-related parameters inpatients with juvenile idiopathic arthritis-associated uveitis

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