Targeted proteomic analysis of aqueous humor in idiopathic uveitis and Vogt Koyanagi Harada syndrome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Xiaomin Zhang
PROVIDER: PXD043575 | iProX | Thu Jul 06 00:00:00 BST 2023
REPOSITORIES: iProX
Similar Datasets
Project description:In this study, 44 AH samples were subjected to a quantitative analysis using SWATH, and 557 proteins were identified in each sample according to a well-established library of 634 proteins. Proteomic profiles in AH of IU and VKH groups were significantly different from normal controls, whereas relatively minor inter-group variation was observed. Differential analysis revealed a shared pattern of extracellular matrix disruption in IU and VKH groups and, more importantly, downregulation of retinal cellular proteins highlighting the value of AH as a medium for ocular disease research. Enrichment analysis showed a typical inflammatory state in the protein composition of AH in IU and VKH groups compared to normal controls, where innate immunity played an important role, as indicated by the activation of the complement cascade and the overexpression of innate immune cell markers. Subsequently, an efficient and robust machine learning algorithm, XGBoost, was used to develop a model for classifying IU, VKH, and normal controls. The top three ranked proteins in the importance list, TF, ENPP2, and FUCA1, were found to represent a promising biomarker panel.
2023-04-04 | PXD041318 |
Project description:To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.
| S-EPMC8782285 | biostudies-literature
Project description:Leptospiral organisms have long been presumed to be associated with the presence of equine recurrent uveitis. This project was undertaken to determine the presence of Leptospira spp. in the aqueous humor of horses with uveitis to determine if there was an association with inflammation. Thirty horses were determined to have recurrent uveitis based on clinical evaluation or history. Sixteen horses were judged clinically and historically to be free of uveitis and were used as controls. Aqueous humor samples were cultured and evaluated by PCR for the presence of Leptospira DNA. Serum was collected and evaluated for the presence of antibodies against five serovars in a leptospirosis panel. Twenty-one of 30 horses with recurrent uveitis and one of 16 uveitis-free horses were positive by PCR for the presence of Leptospira DNA. Six of these 21 horses with uveitis were culture positive for leptospires from the aqueous humor. Serologic results did not correlate well with the presence of Leptospira DNA or organisms in the aqueous humor. Leptospira spp. are present in a high percentage of horses with naturally occurring recurrent uveitis.
| S-EPMC87011 | biostudies-literature
Project description:Non-infectious uveitis are intraocular inflammatory conditions caused by dysregulated activation of the immune response without any detectable infectious agents. The aim of this study was to explore potential markers and therapeutic targets for two distinct types of non-infectious uveitis associated with Behçet's disease (BD) and Vogt Koyanagi Harada (VKH) disease. Concentrations of 27 cytokines were investigated in aqueous humor (AH) samples from patients with active uveitis vs. healthy controls (HC) (n = 10 patients with BD-associated uveitis; n = 10 patients with VKH-associated uveitis; n = 10 HC) using the Bio-Plex ProTM human cytokine group I panel. Additionally, leukocytes in AH samples were counted with hemocytometers and characterized by flow cytometry. Eleven cytokines were differentially expressed between patients with uveitis and HC with a median concentration greater than 10 pg/ml. IL-6, IP-10, G-CSF, and IFNγ showed higher concentrations in AH samples from both BD and VKH patients while IL-2, IL-8, IL-13, TNFα, eotaxin, IL-1ra showed statistically significant higher concentrations only in AH samples from BD patients. GM-CSF was the sole cytokine with an opposite profile showing decreased levels in AH samples from BD patients. IL-1ra and IL-6 were detected at higher frequencies in AH samples from BD and VKH patients compared with those from HC while IFNγ and TNFα were not detected in HC. The concentrations of IL-6, IL-8, IP-10, G-CSF, IFNγ, TNFα, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, suggesting that such cytokines can be produced by immune cells and/or attract and/or promote proliferation and survival of immune cells in these types of uveitis. The correlation matrix of cytokine concentrations in AH samples revealed that IFNγ, TNFα, eotaxin, IL-6, G-CSF highly correlated each other. The ratios of cytokine concentrations between AH and plasma intra-individuals showed that IL-2, IL-6, IP-10, GM-CSF were increased intraocularly. In conclusion, AH sampling followed by multiplex analysis of cytokines should be fostered in non-infectious uveitis to identify cytokines dysregulated intraocularly in each individual laying the groundwork for precision medicine.
| S-EPMC7077343 | biostudies-literature
Project description:Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, as well as with uncontrolled intraocular pressure (IOP) and a subsequent higher requirement for future glaucoma surgery. To gain novel insights into the pathogenesis of ocular hypertension in these patients, we investigated the proteome changes of the aqueous humor (AH) derived from the CMV hypertensive anterior uveitis (CMV-HAU; n = 10) patients and non-glaucoma (cataract; n = 10) patients using liquid chromatography with tandem mass spectrometry. Among a total of 562 proteins identified, fifty and fifteen proteins were significantly elevated and decreased, respectively, in the AH of CMV-HAU patients compared to the control subjects by ≥2 fold. Gene ontology (GO) enrichment and network analyses of elevated proteins revealed that the enrichment of protein was involved in the complement activation, the humoral immune response mediated by the circulating immunoglobulins, proteolysis, and platelet degranulation. In the AH of CMV-HAU, GDF (growth/differentiation factor)-15, the inflammatory marker belonging to the TGF-β superfamily proteins, was significantly increased, while vasorin, an anti-TGF-β protein, levels were decreased. The trabecular meshwork cells infected with CMV exhibited a significantly increased expression of inflammatory markers. Collectively, these data indicate increased complement factor associated inflammation and humoral immunity in CMV-HAU associated ocular hypertension.
| S-EPMC9101446 | biostudies-literature
Project description:We profiled using single cell RNA sequencing the immune cells of the aqueous humor from patients with uveitis.
2023-12-14 | GSE229166 | GEO
Project description:The purpose of this study is to discover genes that might increase aqueous humor outflow when human ciliary muscle or human trabecular meshwork cells are treated with the prostaglandin analogues latanoprost free acid or prostaglandin F2alpha. Five tissue donors were pooled on each chip. Keywords: other
2003-07-16 | GSE492 | GEO
Project description:ObjectiveTo assess the clinical value of aqueous humor real-time polymerase chain reaction (RT-PCR) and serological antibody tests among uveitis patients in Indonesian cohort.MethodsIn this prospective cohort study, single-plex RT-PCR analysis of aqueous samples from 86 new uveitis patients was performed to detect Mycobacterium tuberculosis, Toxoplasmosis gondii, cytomegalovirus, herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and rubella virus. Specific serological antibodies for suspected pathogens were also obtained. Comparison of PCR and serological antibodies with the initial and final diagnosis were presented.ResultsThe diagnostic positivity of aqueous RT-PCR in our cohort was 20% (17/86). The rate of infection as final etiological classification was higher after RT-PCR was performed (45 patients, 52%) compared to initial diagnosis based on clinical presentation alone (38 patients, 44%). In particular, the RT-PCR positivity among patients with infection as the final etiological classification was 33.33% (15/45). A significant difference in the IgG but not IgM toxoplasma value among those with ocular toxoplasmosis as the final diagnosis compared to the other etiologies were observed (3953 (IQR 2707-19562) IU/mL vs 428 (IQR 82-1807) IU/mL; p < 0.0001).ConclusionRT-PCR analysis of aqueous fluid from uveitis patients helped confirm a third of infectious uveitis cases in Indonesia. In ocular toxoplasmosis, high IgG but not IgM antibody value might help differentiate those with other etiology.
| S-EPMC9573923 | biostudies-literature
Project description:BackgroundThis study aims to compare the levels of intraocular cytokines between Fuchs uveitis syndrome (FUS) eyes and the senile cataract eyes. The association between inflammatory cytokine levels and cataract severity in FUS is evaluated to find the possible mechanism of cataract in FUS eyes.MethodsA retrospective study of 28 eyes with FUS was performed. Auxiliary examinations were performed, including ophthalmic examinations, laser flare-cell photometry, and levels of inflammatory cytokines in the aqueous humor were measured. The control group included 25 eyes with senile cataract. Data on the aqueous humor inflammatory cytokines were compared between the two groups. The association between the aqueous humor cytokine levels and severity of posterior subcapsular cataract was assessed.ResultsThere were 28 eyes with FUS in 27 patients. Unilateral involvement was noted in 26 patients (96.30%). Stellate keratic precipitates (KPs) were noted in 16 eyes (57.14%). Heterochromia was observed in 21.43% of affected eyes. Posterior subcapsular cataract (PSC) was observed in 16 of the 28 eyes. Eyes with FUS had significantly higher aqueous humor (AH) cytokine levels (VEGF, bFGF, IL-6, IL-8 and IL-10) compared with the control eyes (P < 0.05). There was a statistically significant positive correlation between the severity of cataract and IL-6 and IL-8 levels in the AH (τ = 0.664 and 0.634, respectively; P = 0.001, P = 0.002, respectively).ConclusionsExpression of VEGF, bFGF, IL-6, IL-8 and IL-10 in the AH of FUS patients was significantly higher than in senile cataract eyes, and the aqueous humor levels of IL-6 and IL-8 were significantly positively associated with the severity of posterior subcapsular cataract. Our results imply that an inflammation mechanism may be involved in the early development of cataract in FUS.
| S-EPMC7912921 | biostudies-literature
Project description:We performed liquid chromatography-tandem mass spectrometry-based proteomic methods to evaluate the aqueous humor protein profiles of all 37 samples.
2023-07-07 | PXD043597 |