RESUMEN
Purpose: To investigate the profiles and correlations between local and systemic inflammatory molecules in patients with retinitis pigmentosa (RP). Methods: The paired samples of aqueous humor and serum were collected from 36 eyes of 36 typical patients with RP and 25 eyes of age-matched patients with cataracts. The concentration of cytokines/chemokines was evaluated by a multiplexed immunoarray (Q-Plex). The correlations between ocular and serum inflammatory molecules and their association with visual function were analyzed. Results: The aqueous levels of IL-6, Eotaxin, GROα, I-309, IL-8, IP-10, MCP-1, MCP-2, RANTES, and TARC were significantly elevated in patients with RP compared to controls (all P < 0.05). The detection rate of aqueous IL-23 was higher in patients with RP (27.8%) compared with controls (0%). In patients with RP, Spearman correlation test demonstrated positive correlations for IL-23, I-309, IL-8, and RANTES between aqueous and serum expression levels (IL-23: â´ = 0.8604, P < 0.0001; I-309: ρ = 0.4172, P = 0.0113; IL-8: ρ = 0.3325, P = 0.0476; RANTES: ρ = 0.6685, P < 0.0001). In addition, higher aqueous IL-23 was associated with faster visual acuity loss in 10 patients with RP with detected aqueous IL-23 (ρ = 0.4119 and P = 0.0264). Multiple factor analysis confirmed that aqueous and serum IL-23 were associated with visual acuity loss in patients with RP. Conclusions: These findings suggest that ocular and systemic inflammatory responses have a close interaction in patients with RP. Further longitudinal studies with larger cohorts are needed to explore the correlation between specific inflammatory pathways and the progression of RP. Translational Relevance: This study demonstrates the local-systemic interaction of immune responses in patients with RP.
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Humor Acuoso , Citocinas , Retinitis Pigmentosa , Humanos , Femenino , Masculino , Retinitis Pigmentosa/sangre , Humor Acuoso/metabolismo , Humor Acuoso/inmunología , Persona de Mediana Edad , Adulto , Citocinas/sangre , Anciano , Biomarcadores/sangre , Agudeza Visual , Quimiocinas/sangreRESUMEN
Purpose: To investigate the effects of anterior chamber pigment dispersion on ocular immune privilege and the possible mechanisms involved in a DBA/2J mouse model of pigmentary glaucoma. Methods: DBA/2J mice were utilized as a pigment dispersion model, and age-matched C57BL/6J mice were used as the control group in this study. Proteins in the aqueous humor (AH) and serum were quantified using the bicinchoninic acid assay. Immune cells in the AH were detected using hematoxylin and eosin staining and immunocytochemistry. The expression of TGF-ß2 in the AH and cytokine levels (IL-10, IFN-γ) in serum were measured using ELISA. Anterior chamber-associated immune deviation (ACAID) was induced in DBA/2J mice by injecting antigens into the anterior chamber. Delayed-type hypersensitivity (DTH) assays were used to assess the induction of ACAID. In DBA/2J mice, before and after pigment dispersion, following anterior chamber injection of pigment particles, and after ACAID modeling, the expression of regulatory T cells (Tregs) was detected using flow cytometry. Results: Compared to C57BL/6J mice, the protein concentration, immune cell count, and TGF-ß2 levels in the AH were elevated in DBA/2J mice. Protein concentration and IL-10 levels in serum were increased, while IFN-γ levels were decreased in DBA/2J. Additionally, the expression of Treg cells in the spleen of DBA/2J mice was significantly increased after pigment dispersion and anterior chamber injection of pigment particles. At 3 and 6 months, DTH responses in DBA/2J mice were not inhibited, thus preventing ACAID induction. However, the opposite was observed at 9 months in DBA/2J mice. Furthermore, the ACAID group exhibited an augmented expression of Treg cells. Conclusions: Dispersion of pigment particles in the anterior chamber of the eye enhances the state of ocular immune privilege by influencing the immunosuppressive microenvironment and inducing more Treg cells to reestablish ACAID.
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Humor Acuoso , Modelos Animales de Enfermedad , Glaucoma de Ángulo Abierto , Privilegio Inmunológico , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Linfocitos T Reguladores , Animales , Humor Acuoso/metabolismo , Humor Acuoso/inmunología , Ratones , Linfocitos T Reguladores/inmunología , Glaucoma de Ángulo Abierto/inmunología , Cámara Anterior/inmunología , Factor de Crecimiento Transformador beta2 , Presión Intraocular/fisiología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Interleucina-10 , Hipersensibilidad Tardía/inmunología , Interferón gamma/metabolismo , Inmunohistoquímica , FemeninoRESUMEN
Th17/Treg cell balance is essential for immune homeostasis and when disrupted, is associated with the occurrence and development of inflammation in numerous autoimmune diseases. However, its contribution in pathophysiology of uveitis remains unexplored. In this study, we deciphered the role of Th17/Treg cell balance in autoimmune uveitis subjects. Using flow cytometry, we detected the frequencies and absolute count of both Th17 and Treg cells in the aqueous humor and peripheral blood of patients and healthy controls. Our results for the first time reveal a significant increase (p < 0.01 and p < 0.005) in Th17 population alongside a significant decrease (p < 0.001 and p < 0.003) in Treg cell population in both the aqueous humor and PBMCs of uveitis patients. Further we analyzed the expression of Th17-Treg associated genes and cytokines via qPCR and ELISA respectively. These findings align with our flow cytometry results, as evident by a significant (p < 0.002) up-regulation of IL-17 and a concurrent down regulation of IL-10 at transcriptional levels. Moreover, IL-17A cytokine was found to be substantially high (p < 0.001) and IL-10 (p < 0.02) down regulated in serum. Interestingly, we demonstrated a significant correlation of Th17/Treg cells in aqueous humor with those in peripheral blood. Conclusively, our results suggest the pivotal role of Th17/Treg cell axis in the immuno-pathophysiology of human uveitis. Further we propose the therapeutic potential of targeting this novel axis for ameliorating the disease burden associated with uveitis.
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Humor Acuoso , Linfocitos T Reguladores , Células Th17 , Uveítis Intermedia , Humanos , Células Th17/inmunología , Células Th17/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Femenino , Masculino , Adulto , Humor Acuoso/inmunología , Humor Acuoso/metabolismo , Uveítis Intermedia/inmunología , Uveítis Intermedia/diagnóstico , Citocinas/metabolismo , Persona de Mediana Edad , Adulto JovenRESUMEN
Background: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in older people. Low-grade inflammation is well-known as one of the pathogenic mechanisms in nAMD. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for nAMD, although macula atrophy (MA) developed under anti-VEGF therapy causes irreversible visual function impairment and is recognized as a serious disorder. Here, we show specific expression patterns of aqueous humor (AH) cytokines in nAMD eyes developing MA under intravitreal injection of aflibercept (IVA) as an anti-VEGF antibody and present predictive cytokines as biomarkers for the incidence of MA in nAMD eyes under IVA treatment. Methods: Twenty-eight nAMD patients received three consecutive monthly IVA, followed by a pro re nata regimen for 2 years. AH specimens were collected before first IVA (pre-IVA) and before third IVA (post-IVA). AH cytokine levels, visual acuity (VA), and central retinal thickness (CRT) were measured. Results: Two-year incidence of MA was 21.4%. In nAMD eyes developing MA [MA (+) group], pre-IVA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1ß, VEGF and post-IVA level of MCP-1 were higher than those in nAMD eyes without MA [MA (-) group]. In hierarchical cluster analysis, pre-IVA MCP-1 and VEGF were grouped into the same subcluster, as were post-IVA MCP-1 and CRT. In principal component analysis, principal component loading (PCL) of pre-IVA interferon-γ-inducible protein 10 (IP-10) was 0.61, but PCL of post-IVA IP-10 decreased to -0.09. In receiver operating characteristic analysis and Kaplan-Meier curves, pre-IVA MCP-1, MIP-1ß, and VEGF and post-IVA interleukin-6, MCP-1, and MIP-1ß were detected as predictive factors for MA incidence. In 2-year clinical course, changes of VA in groups with high levels of pre-IVA MIP-1ß (over 39.9 pg/ml) and VEGF (over 150.4 pg/ml) were comparable to those in MA (+) group. Conclusion: Substantial loss of IP-10 effects and persistent inflammation contribute to incidence of MA, and screening of AH cytokine levels could be a useful method to predict MA incidence in nAMD eyes under anti-VEGF therapy.
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Inhibidores de la Angiogénesis/efectos adversos , Humor Acuoso/metabolismo , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Mácula Lútea/efectos de los fármacos , Degeneración Macular/tratamiento farmacológico , Proteínas Recombinantes de Fusión/efectos adversos , Neovascularización Retiniana , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Humor Acuoso/inmunología , Atrofia , Biomarcadores/metabolismo , Femenino , Humanos , Inyecciones Intravítreas , Mácula Lútea/inmunología , Mácula Lútea/metabolismo , Mácula Lútea/patología , Degeneración Macular/inmunología , Degeneración Macular/metabolismo , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Agudeza Visual/efectos de los fármacosRESUMEN
The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.
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Quimiocina CCL2/metabolismo , Infecciones Virales del Ojo/inmunología , Interleucina-8/metabolismo , Malla Trabecular/citología , Uveítis Anterior/virología , Adulto , Humor Acuoso/inmunología , Movimiento Celular , Células Cultivadas , Citomegalovirus/patogenicidad , Proteínas de la Matriz Extracelular/metabolismo , Infecciones Virales del Ojo/patología , Herpesvirus Humano 1/patogenicidad , Humanos , Persona de Mediana Edad , Cultivo Primario de Células , Receptores CCR2/metabolismo , Receptores de Interleucina-8A/metabolismo , Malla Trabecular/inmunología , Malla Trabecular/virología , Uveítis Anterior/inmunología , Uveítis Anterior/patologíaRESUMEN
BACKGROUND: To evaluate the correlations between the inflammatory factors in the aqueous humor and hyperreflective foci (HRF) in patients with intractable macular edema treated with antivascular endothelial growth factor (anti-VEGF). METHODS: This study included 17 patients with intractable macular edema (ME) treated with anti-VEGF agents. Inflammatory factors in the aqueous humor were measured by the Cytometric Beads Array before injection, and the numbers of HRF pre- and post-anti-VEGF treatment were counted from four different directions (90 degrees, 45 degrees, 180 degrees, and 135 degrees) in the SD-OCT images, respectively, before treatment and one month after treatment. The correlations between inflammatory factors and the numbers of HRF were assessed. RESULTS: The numbers of HRF were reduced significantly after anti-VEGF treatment. The change in the HRFs at the 90-degree location was significantly positively correlated with IL-8 and VCAM-1. The change of all HRFs was significantly positively correlated with IL-8. The HRFs before the treatment also had a positive correlation with IL-8 and VCAM-1. CONCLUSION: After anti-VEGF treatment, the numbers of HRF in intractable ME declined greatly. The higher the levels of IL-8 and VCAM-1 before treatment, the more significant the reduction of HRF after anti-VEGF treatment, which indicated that HRF could be an effective noninvasive imaging indicator for evaluating the effect of anti-VEGF on intractable macular edema. The OCT images at the 90-degree location could better show the inflammatory reaction of patients and also had better clinical significance for the prognosis evaluation of ME associated with inflammation.
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Inhibidores de la Angiogénesis/administración & dosificación , Humor Acuoso/inmunología , Interleucina-8/metabolismo , Edema Macular/tratamiento farmacológico , Molécula 1 de Adhesión Celular Vascular/metabolismo , Anciano , Inhibidores de la Angiogénesis/farmacología , Humor Acuoso/diagnóstico por imagen , Humor Acuoso/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Edema Macular/diagnóstico por imagen , Edema Macular/inmunología , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Purpose: Agonistic ß2-adrenergic receptor autoantibodies (ß2-agAAbs) were recently observed in sera of patients with ocular hypertension (OHT), primary (POAG), and secondary open-angle glaucoma (SOAG), yet not in healthy controls (HCs). It was the aim of the present study to investigate the presence of ß2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding ß2-agAAb serum data. Material and Methods: Thirty-nine patients (21 male, 18 female) were recruited from the Department of Ophthalmology, University of Erlangen-Nürnberg: twenty-one POAG, 18 SOAG. Aqueous humor samples were collected during minimal invasive glaucoma surgery. Serum and AH samples were analyzed for ß2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U). Results: Thirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a ß2-agAAb in their sera and AH samples, respectively. All ß2-agAAb AH-positive OAG patients were also seropositive. We also observed a ß2-agAAb seropositivity in 95 and 89% of patients with POAG and SOAG, respectively. Beta2-agAAbs were seen in 86% (POAG) and 78% (SOAG) of AH samples. The ß2-agAAb adrenergic activity was increased in the AH of patients with POAG (6.5 ± 1.5 U) when compared with those with SOAG (4.1 ± 1.1 U; p = 0.004). Serum ß2-agAAb adrenergic activity did not differ between the cohorts [POAG (4.5 ± 1.5 U); SOAG (4.6 ± 2.1 U; p=0.458)]. No correlation of the beating rates were observed between serum and AH samples for group and subgroup analyses. Conclusion: The detection of ß2-agAAb in systemic and local circulations supports the hypothesis of a direct functional impact of these agAAbs on ocular G-protein coupled receptors. The high prevalence of ß2-agAAb in serum and AH samples of patients with POAG or SOAG suggests a common role of these AAbs in the etiopathogenesis of glaucoma, independent of open-angle glaucoma subtype.
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Agonistas de Receptores Adrenérgicos beta 2/inmunología , Humor Acuoso/inmunología , Autoanticuerpos/inmunología , Glaucoma de Ángulo Abierto/inmunología , Receptores Adrenérgicos beta 2/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Humor Acuoso/fisiología , Autoanticuerpos/sangre , Autoanticuerpos/farmacología , Células Cultivadas , Femenino , Glaucoma de Ángulo Abierto/sangre , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Ratas Sprague-DawleyRESUMEN
Purpose: To establish a murine model of primary acquired ocular toxoplasmosis (OT) and to investigate the immune mediator profiles in the aqueous humor (AH). Methods: C57BL/6 mice were perorally infected with Toxoplasma gondii. The ocular fundus was observed, and fluorescein angiography (FA) was performed. The AH, cerebrospinal fluid (CSF), and serum were collected before infection and at 28 days post-infection (dpi); the immune mediator levels in these samples were analyzed using multiplex bead assay. Results: Fundus imaging revealed soft retinochoroidal lesions at 14 dpi; many of these lesions became harder by 28 dpi. FA abnormalities, such as leakage from retinal vessels and dilation and tortuosity of the retinal veins, were observed at 14 dpi. Nearly all these abnormalities resolved spontaneously at 28 dpi. In the AH, interferon-γ, interleukin (IL)-1α, IL-1ß, IL-6, IL-10, IL-12(p40), IL-12(p70), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES, and CXCL1/KC levels increased after infection. All these molecules except IL-1α, IL-4, and IL-13 showed almost the same postinfection patterns in the CSF as they did in the AH. The tumor necrosis factor α, IL-4, and IL-5 levels in the AH and CSF of the T. gondii-infected mice were lower than those in the serum. The postinfection IL-1α, IL-6, CCL2/MCP-1, CCL4/MIP-1ß, and granulocyte colony-stimulating factor levels in the AH were significantly higher than those in the CSF and serum. Conclusions: A murine model of primary acquired OT induced via the natural infection route was established. This OT model allows detailed ophthalmologic, histopathologic, and immunologic evaluations of human OT. Investigation of AH immune modulators provides new insight into OT immunopathogenesis.
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Humor Acuoso/inmunología , Modelos Animales de Enfermedad , Angiografía con Fluoresceína , Factores Inmunológicos/metabolismo , Toxoplasmosis Ocular/diagnóstico , Animales , Barrera Hematorretinal , Encéfalo/parasitología , Líquido Cefalorraquídeo/metabolismo , Citocinas/sangre , Técnica del Anticuerpo Fluorescente Indirecta , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Retina/parasitología , Toxoplasma/fisiología , Toxoplasmosis Ocular/inmunologíaRESUMEN
Purpose: To assess the immune status of acute retinal necrosis (ARN) patients and to investigate the immune cell types involved in the immunopathogenesis.Methods: Peripheral blood and intraocular fluid were collected from 17 ARN patients and 9 control subjects. The Percentage of immune cells was measured using flow cytometry, levels of complement and antibodies were determined by rate nephelometry, and cytokine levels in the serum and aqueous humor (AH) were detected using cytokine quantitative chips. Data were analyzed using SPSS 23.0. p < .05 was considered statistically significant.Results: Proportion of T-helper 17 cells (p = .034) in serum and concentrations of multiple cytokines associated with Th17 cells (IL-6, IL-17, IL-17 F, IL-21, IL-22) in AH and serum were elevated of ARN patients.Conclusion: Th17 cells appeared to participate in the development of ARN. We found inflammatory cytokines and cells were elevated in the serum and AH of ARN patients.
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Citocinas/metabolismo , Síndrome de Necrosis Retiniana Aguda/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Anciano , Humor Acuoso/inmunología , Estudios de Casos y Controles , Complemento C3/inmunología , Complemento C4/inmunología , Estudios Transversales , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Infecciones Virales del Ojo/inmunología , Infecciones Virales del Ojo/virología , Femenino , Citometría de Flujo , Herpes Zóster Oftálmico/inmunología , Herpes Zóster Oftálmico/virología , Humanos , Inmunidad Celular , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría , Síndrome de Necrosis Retiniana Aguda/virologíaRESUMEN
AIMS: We evaluate whether the serum and aqueous humour (AH) level of IgG anti-Hsp70.1 antibodies improved the biological diagnosis of ocular toxoplasmosis. METHODS AND RESULTS: In this prospective cross-sectional and multicentre study, serum and AH were collected at the time of active uveitis. Anti-Hsp70.1-antibody levels were determined by ELISA. Patients with confirmed (Group A1, n = 21) or suspected ocular toxoplasmosis (group A2, n = 30) were enrolled, as well as a control group of patients with cataract (group B, n = 42). Serum IgG anti-Hsp70.1 antibody levels were not significantly different within the group of uveitis patients (A1, n = 21 vs A2, n = 30, P = .8) and were significantly associated with the affected retinal zone (P = .006) and with the size of the retinal lesion (P = .03). Serum anti-Hsp70.1 antibody level was positive in 10 out of the 18 patients of group A2. Significant anti-Hsp-70.1 antibody level in AH was reported in only three patients (3 eyes) with confirmed ocular toxoplasmosis. CONCLUSION: While the level of IgG anti-Hsp-70.1 antibody in AH did not improve the laboratory diagnosis of ocular toxoplasmosis, its level in serum was of major significance for retinal damage diagnosis.
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Anticuerpos Antiprotozoarios/análisis , Humor Acuoso/inmunología , Proteínas HSP70 de Choque Térmico/inmunología , Inmunoglobulina G/análisis , Toxoplasmosis Ocular/inmunología , Adulto , Anticuerpos Antiprotozoarios/inmunología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Toxoplasma/inmunología , Toxoplasmosis Ocular/diagnóstico , Uveítis/diagnóstico , Uveítis/inmunologíaRESUMEN
In cataract surgery, it is often found that patients infected hepatitis B virus (HBV) are likely to suffer from more pain than other patients. In order to assess the inflammation status of the aqueous humor in the eyes of cataract patients infected with HBV. RayBio Human Inflammation Array was used to assay aqueous humor samples collected from 14 eyes of patients infected with HBV and 14 eyes of cataract patients without HBV infection (the controls) during the cataract surgery. RayBio Human Quantibody Cutom Array was adopted for the validation of the screened cytokines, with aqueous humor samples collected from 40 eyes of patients infected with HBV and 40 eyes of the controls. A pain questionnaire survey about the surgery was conducted in all patients after operation. The results of questionnaire showed that patients infected with HBV were more likely to have pain during operation. The Human Inflammation Array revealed that the expression levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α) and tumor necrosis factor ß (TNF-ß) were very high in HBV infected patients and IL-1ra was much lower in patients infected with HBV (all, P < 0.05). In validation, the Human Quantibody Cutom Array revealed that the expression levels of MCP-1 and TNF-α were high in HBV infected patients with significant difference (all P < 0.05). These results revealed that pain-related inflammatory factors MCP-1 and TNF-α were increased in aqueous humor of cataract patients infected with HBV, which indicates that patients infected with HBV may be more prone to intraoperative pain.
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Humor Acuoso/inmunología , Catarata/complicaciones , Catarata/inmunología , Citocinas/metabolismo , Hepatitis B/complicaciones , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Dolor/epidemiologíaRESUMEN
In this retrospective, single-center, observational study, we compared the clinical characteristics, analyzed the glaucoma development, and the glaucoma surgery requirement mediators in patients with different virus-associated anterior uveitis (VAU). In total, 270 patients (= eyes) with VAU confirmed by positive Goldmann-Witmer coefficients (GWC) for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubella virus (RV), and multiple virus (MV) were included. Clinical records of these patients were analyzed. Demographic constitution, clinical findings, glaucoma development, and surgeries were recorded. The concentrations of 27 immune mediators were measured in 150 samples of aqueous humor. The GWC analysis demonstrated positive results for CMV in 57 (21%), HSV in 77 (29%), VZV in 45 (17%), RV in 77 (29%), and MV in 14 (5%) patients. CMV and RV AU occurred predominantly in younger and male patients, while VZV and HSV AU appeared mainly with the elderly and females (P<0.0001). The clinical features of all viruses revealed many similarities. In total, 52 patients (19%) showed glaucomatous damage and of these, 27 patients (10%) needed a glaucoma surgery. Minimal-invasive glaucoma surgery (MIGS) showed a reliable IOP reduction in the short-term period. In 10 patients (37%), the first surgical intervention failed and a follow-up surgery was required. We conclude that different virus entities in anterior uveitis present specific risks for the development of glaucoma as well as necessary surgery. MIGS can be suggested as first-line-treatment in individual cases, however, the device needs to be carefully chosen by experienced specialists based on the individual needs of the patient. Filtrating glaucoma surgery can be recommended in VAU as an effective therapy to reduce the IOP over a longer period of time.
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Glaucoma/cirugía , Uveítis Anterior/virología , Adulto , Factores de Edad , Humor Acuoso/inmunología , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/virología , Femenino , Glaucoma/etiología , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Retrospectivos , Factores Sexuales , Uveítis Anterior/diagnósticoRESUMEN
Atopic cataracts develop under the ages of 40 years, after which visual acuity rapidly declines. However, the mechanism underlying the development of atopic cataracts is not yet clear. We focused on the eosinophil granule major basic protein (MBP), which was detected in the aqueous humor of atopic cataracts previously, and which was cytotoxic. Specifically, we investigated its origin in this fluid and its effects on lens epithelial cells (LECs). MBP immunostaining was positive in atopic cataract-derived LECs, but negative in age-related cataract-derived LECs. MBP mRNA was not detected in either type of cataract, but protein was detected in the aqueous humor. Furthermore, the flare values associated with atopic cataracts were higher than those with age-related cataracts. When MBP was purified from eosinophils or recombinant MBP was added to LEC culture medium, cell viability decreased in a concentration-dependent manner, but an MBP antibody neutralized the cytotoxic effect of this protein towards these cells. These results were consistent with the flow of MBP into the aqueous humor from the blood due to a compromised blood-aqueous barrier. Thus, MBP could further penetrate the lens capsule and adhere to LECs, resulting in decreased cell viability and the development of atopic cataracts.
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Catarata/inmunología , Proteína Mayor Básica del Eosinófilo/metabolismo , Eosinófilos/metabolismo , Proteoglicanos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humor Acuoso/inmunología , Humor Acuoso/metabolismo , Estudios de Casos y Controles , Catarata/sangre , Catarata/patología , Extracción de Catarata , Supervivencia Celular/inmunología , Células Cultivadas , Proteína Mayor Básica del Eosinófilo/análisis , Proteína Mayor Básica del Eosinófilo/inmunología , Proteína Mayor Básica del Eosinófilo/aislamiento & purificación , Eosinófilos/inmunología , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino , Humanos , Cristalino/citología , Cristalino/inmunología , Cristalino/patología , Cristalino/cirugía , Masculino , Cultivo Primario de Células , Proteoglicanos/análisis , Proteoglicanos/inmunología , Proteoglicanos/aislamiento & purificación , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Adulto JovenRESUMEN
To investigate aqueous cytokine profiles in acute anterior uveitis (AAU), Fuchs' syndrome, Vogt-Koyanagi-Harada (VKH) disease and Behcet's disease (BD), we assayed the concentrations of 17 cytokines by multiplex immunoassay in aqueous humor (AqH) collected during cataract surgery from 24 AAU, 29 Fuchs' syndrome, 29 VKH disease, 30 BD and 30 senile cataract control patients. Aqueous cytokine levels were compared between the five groups and analysed by logistic regression. Cytokine levels were then compared between uveitis patients who underwent cataract surgery within 3â¯months and those who underwent this surgery more than 3â¯months after complete control of intraocular inflammation. The results showed that aqueous levels of interferon (IFN)-γ, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1ß and tumour necrosis factor (TNF)-α levels in AqH from patients with Fuchs' syndrome were significantly higher than those in the other four groups. Using multivariate analysis, MIP-1ß was found to be significantly associated with Fuchs' syndrome. There was no difference in aqueous cytokine levels between cases having cataract surgery within 3â¯months compared to those after 3â¯months of complete control of their intraocular inflammation. The current study shows that Chinese patients with Fuchs' syndrome appear to have a specific cytokine profile. MIP-1ß is an important chemokine in the intraocular environment of Fuchs' syndrome. Aqueous cytokine profiles support the performance of cataract surgery in uveitis within 3â¯months after intraocular inflammation control.
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Humor Acuoso/metabolismo , Síndrome de Behçet/inmunología , Citocinas/metabolismo , Uveítis Anterior/inmunología , Síndrome Uveomeningoencefálico/inmunología , Adulto , Anciano , Humor Acuoso/inmunología , Síndrome de Behçet/complicaciones , Síndrome de Behçet/patología , Catarata/etiología , Catarata/inmunología , Extracción de Catarata , Citocinas/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Uveítis Anterior/complicaciones , Uveítis Anterior/patología , Síndrome Uveomeningoencefálico/complicaciones , Síndrome Uveomeningoencefálico/patología , Adulto JovenRESUMEN
Neovascular age-related macular degeneration (nAMD) is a complex and multi-factorial disease, and low-grade inflammation is associated with pathogenesis of nAMD. Aqueous humor could reflect intraocular immune environments in various eye diseases. The research so far used aqueous humor samples and revealed that inflammation is involved in pathophysiology of nAMD, although immunological roles of cytokines were evaluated inadequately with aspect to individual effects. Here we used 27 kinds of cytokines covering general immunologic reactions, examined specific expression patterns of cytokines, and assessed relationships between inflammation and pathophysiology of nAMD by multivariate analyses. In nAMD eyes, principal component analysis showed that IL-7, MCP-1, MIP-1ß and VEGF had high principal component loadings of over 0.6 in the first principal component constituting 32.6% of all variability of the data. In exploratory factor analysis, IL-6, MCP-1 and MIP-1ß had high factor loadings (FL) of over 0.5 in Factor 1 constituting 32.6% of all variability, while VEGF had FL of over 1.0 in Factor 3 constituting 10.7% of all variability. In hierarchical cluster analysis, MCP-1 and VEGF were located in the cluster of first proximate mutual distance to central retinal thickness. These data could suggest that low-grade inflammation is a principal contributor in nAMD.
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Humor Acuoso/metabolismo , Neovascularización Coroidal/complicaciones , Citocinas/metabolismo , Degeneración Macular/inmunología , Neovascularización Retiniana/complicaciones , Anciano , Anciano de 80 o más Años , Humor Acuoso/inmunología , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/inmunología , Citocinas/inmunología , Femenino , Angiografía con Fluoresceína , Perfilación de la Expresión Génica , Humanos , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Retina/diagnóstico por imagen , Retina/inmunología , Retina/patología , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/inmunología , Neovascularización Retiniana/patología , Vasos Retinianos/patología , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To evaluate the relationship between the aqueous humor levels of VEGF, TNF-α, IL-10, IL-6, IL-12, MCP-1, and IP-10 with DR/DME. METHODS: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched up to October 2018. Systematic review and meta-analysis were conducted. RESULTS: 18 studies comprising 362 cases with DR (100 with DME) and 620 controls without DR were included in this meta-analysis. There was a significant association between VEGF levels in the aqueous humor and DR (standardized mean difference (SMD) 1.94 (95% CI 1.05-2.83)) and DME (1.07 (0.71, 1.42)). Furthermore, a significant correlation was observed between levels of IL-6 and DR (3.53 (0.37, 6.69)), and similarly correlation with DME (1.26 (0.30, 2.21)). The relationship between MCP-1 and DR and DME was significant, in which the SMD was (0.49 (0.09, 0.89)) and (1.49 (0.78, 2.20)), respectively. However, IL-12, IP-10, and TNF-α had no correlation with DR and DME, whereas there was a significant relationship between IL-8 and DME (1.68 (0.97, 2.40)). CONCLUSION: Elevated levels of VEGF, IL-6, and MCP-1 in the aqueous humor were associated with the risk for the presence of DR, and levels of VEGF, IL-6, IL-8, and MCP-1 were associated with the risk of DME. Furthermore, these biomarkers may be used as potential predictors or therapeutic targets for DR/DME.
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Humor Acuoso/inmunología , Citocinas/metabolismo , Complicaciones de la Diabetes/epidemiología , Retinopatía Diabética/epidemiología , Edema Macular/epidemiología , Biomarcadores/metabolismo , Complicaciones de la Diabetes/inmunología , Retinopatía Diabética/inmunología , Femenino , Humanos , Edema Macular/inmunología , MasculinoRESUMEN
Glaucoma eventually leads to optic nerve damage and vision loss without medical intervention. More than 50% of glaucoma caused blindness are attributed to primary angle closure glaucoma, particularly in Asians. It is reported that immune inflammation is involved in the progress of glaucoma. Increased inflammation cytokines are detected in the aqueous humor of chronic primary angle closure glaucoma (CPACG). IL-36, IL-37 and IL-38, are novel cytokines and are involved in many inflammatory diseases, including inflammatory bowel diseases and acute anterior uveitis, but the possible contributing role in the pathogenesis of CPACG is unclear. In our current study, increased IL-36, IL-37 and IL-38 were detected in the aqueous humor of CPACG compared with age-related cataract (ARC). Furthermore, a significant correlation was detected between mean deviation of visual field (MDVF) of CPACG and IL-36, IL-37 or IL-38, respectively. Our data suggest IL-36, IL-37 and IL-38 might contribute to the immunological mediated pathogenesis of CPACG, despite the eye being an immune-privileged organ under normal conditions. The precise underlying mechanism of these cytokines during the development of CPACG remains to be explored. Our findings may be useful in therapeutic targeting of specific pathology.
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Humor Acuoso/metabolismo , Glaucoma de Ángulo Cerrado/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-1/metabolismo , Interleucinas/metabolismo , Visión Ocular/inmunología , Anciano , Anciano de 80 o más Años , Humor Acuoso/inmunología , Enfermedad Crónica , Femenino , Humanos , Degeneración Macular/inmunología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
PURPOSE: To compare the intraocular cytokine and chemokine profiles in patients with acute primary acquired ocular toxoplasmosis (pOT) or recurrent ocular toxoplasmosis (rOT) and to correlate them with their clinical characteristics. METHODS: Aqueous humor samples were collected from 62 consecutive patients (21 pOT, 30 rOT, and 11 noninfected controls) and analyzed by multiplex assay. Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (Th1, Th2, and Th17), and clinical characteristics. In all OT patients, the clinical diagnosis of either pOT or rOT was confirmed by positive intraocular Goldmann/Witmer-Desmonts coefficient. Correlations were assessed between a preselected panel of immune mediators and the clinical characteristics of OT. RESULTS: In pOT patients, increased levels of IL-2, IFN-γ, TNF-α, IL-15, IL-4, IL-5, IL-9, IL-13, IL-17, IL-1Rα, IL-6, IL-1ß, and chemokines MIP-1α, MIP-1ß, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, GM-CSF, G-CSF, and MCP-1 were found in comparison to those in controls (p < 0.05). Patients with rOT showed elevated levels of IL-2, IFN-γ, TNF-α, IL-15, IL-4, IL-5, IL-9, IL-17, IL-1Rα, IL-6, IL-1ß, and chemokines MIP-1α, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, G-CSF, and MCP-1 compared to controls (p < 0.05). In addition, IL-7 (p = 0.028) differed between pOT and rOT; IL-9 (p = 0.054) and IL-13 (p = 0.051) showed a tendency of higher concentration in pOT than in rOT. A negative correlation was found between IL-7 (p = 0.017) as well as IL-9 (p = 0.008) and the number of recurrences. Cytokine ratios showed no difference between pOT and rOT, indicating a dominant Th1-type response in both infectious groups. Moreover, a positive correlation was detected between IL-7, VEGF, IL-13 and age at aqueous humor sampling (p < 0.05). CONCLUSIONS: This study for the first time shows subtle differences between the intraocular cytokine profiles in patients with either acute pOT or rOT.
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Humor Acuoso/metabolismo , Toxoplasmosis Ocular/metabolismo , Adulto , Anciano , Humor Acuoso/inmunología , Quimiocinas/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Toxoplasmosis Ocular/inmunologíaRESUMEN
Gene and protein expression profiles of iris biopsies, aqueous humor (AqH), and sera in patients with juvenile idiopathic arthritis-associated uveitis (JIAU) in comparison to control patients with primary open-angle glaucoma (POAG) and HLA-B27-positive acute anterior uveitis (AAU) were investigated. Via RNA Sequencing (RNA-Seq) and mass spectrometry-based protein expression analyses 136 genes and 56 proteins could be identified as being significantly differentially expressed (DE) between the JIAU and POAG group. Gene expression of different immunoglobulin (Ig) components as well as of the B cell-associated factors ID3, ID1, and EBF1 was significantly upregulated in the JIAU group as compared to POAG patients. qRT-PCR analysis showed a significantly higher gene expression of the B cell-related genes CD19, CD20, CD27, CD138, and MZB1 in the JIAU group. At the protein level, a significantly higher expression of Ig components in JIAU than in POAG was confirmed. The B cell-associated protein MZB1 showed a higher expression in JIAU patients than in POAG which was confirmed by western blot analysis. Using bead-based immunoassay analysis we were able to detect a significantly higher concentration of the B cell-activating and survival factors BAFF, APRIL, and IL-6 in the AqH of JIAU and AAU patients than in POAG patients. The intraocularly upregulated B cell-specific genes and proteins in iris tissue suggest that B cells participate in the immunopathology of JIAU. The intracameral environment in JIAU may facilitate local effector and survival functions of B cells, leading to disease course typical for anterior uveitis.
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Humor Acuoso/inmunología , Artritis Juvenil/inmunología , Proteínas del Ojo/inmunología , Regulación de la Expresión Génica/inmunología , Iris/inmunología , Transcriptoma/inmunología , Uveítis/inmunología , Adolescente , Adulto , Anciano , Artritis Juvenil/complicaciones , Artritis Juvenil/patología , Niño , Preescolar , Femenino , Humanos , Iris/patología , Masculino , Persona de Mediana Edad , Proteómica , Uveítis/etiología , Uveítis/patologíaRESUMEN
PURPOSE: Evidence exists that the interleukin (IL)-10 family of cytokines is involved in autoimmune diseases. The aim of this study was to analyse the levels of the IL-10 family cytokines IL-10, IL-19, IL-20, IL-22, IL-26, IL-28A and IL-29 in aqueous humour (AH) samples from patients with specific uveitic entities. In addition, we correlated their levels with the levels of the proinflammatory cytokines tumour necrosis factor-α (TNF-α) and IL-1ß. METHODS: Aqueous humour (AH) samples from patients with active uveitis associated with Behçet's disease (BD; n = 13), sarcoidosis (n = 8), human leucocyte antigen (HLA)-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12) and control subjects (n = 9) were assayed with the use of a multiplex assay. RESULTS: Of all the IL-10 family cytokines studied, only IL-19 levels were significantly higher in AH samples of patients (n = 45) than in controls (p = 0.022). When comparing the four individual disease groups to controls, IL-19 levels were only significantly higher in HLA-B27-associated uveitis (p < 0.001). IL-19 levels were significantly higher in patients with HLA-B27-associated uveitis than in patients with BD, sarcoidosis and VKH disease (p < 0.001; p = 0.002; p < 0.001, respectively). Significant correlations were found between AH levels of IL-19 and AH levels of TNF-α, (r = 0.3; p = 0.03) and IL-1ß (r = 0.56; p < 0.001). CONCLUSIONS: Among the IL-10 family cytokines analysed, IL-19 demonstrated the highest expression in endogenous uveitis, particularly in HLA-B27-associated uveitis. IL-19 thus might assist in the regulation of inflammation in HLA-B27-associated uveitis.