RESUMEN
Purpose: The purpose of this study was to investigate the levels of cytokines in the vitreous, and their correlation with the density of inflammatory cells in fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR) to evaluate intraocular inflammatory conditions with regard to disease activity. Methods: Thirty-three patients (33 eyes) with PDR requiring vitreoretinal surgery because of FVMs and tractional detachment were enrolled in the study, and compared with 20 patients (20 eyes) with macular hole (MH; control group). All patients underwent complete ophthalmological examinations before surgery. The activity of the disease was noted in patients with PDR. Samples of vitreous and blood were taken, and cytokine (MCP-1, IL-8, IL-6, VEGF, IL-1ß, TNF-α, MIP-1α, MIP-1ß, IL-10, and IL-12) levels were measured using cytometric bead array (CBA). Samples of FVMs were analyzed with immunohistochemical methods for the presence of inflammatory cells (CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells), and the numerical areal density was calculated (NA). Spearman's correlation was used to assess the association between variables. The Mann-Whitney test was used to assess the differences between independent groups. The Wilcoxon signed-rank test was used for assessing differences between two related groups. A p value of less than 0.05 was considered statistically significant. Results: Patients with active PDR had statistically significantly higher levels of MCP-1 (p = 0.003), VEGF (p = 0.009), and IL-8 (p = 0.02) in the vitreous in comparison with those with inactive PDR. CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells were identified in FVMs for patients with PDR. Statistically significantly higher numerical areal density of T lymphocytes (CD3+, CD4+, and CD8+) was demonstrated in patients with active PDR in comparison with patients with inactive PDR. Moderate to strong correlations were found between either MCP-1 or IL-8 in the vitreous, and the numerical areal density of cells (CD45+, CD3+, CD4+, and CD8+) in the FVMs, and weaker between either MCP-1 or IL-8 in the vitreous and the numerical areal density of CD14+ cells in the FVMs. Conclusions: The correlation of cytokine (MCP-1 and IL-8) vitreous levels with the density of inflammatory cells in FVMs, and differences in cytokine levels in the vitreous between patients with active and inactive PDR, and between the vitreous and serum in PDR indicate the importance of local intraocular inflammation in patients with PDR.
Asunto(s)
Quimiocina CCL2/inmunología , Retinopatía Diabética/inmunología , Interleucina-8/inmunología , Perforaciones de la Retina/inmunología , Linfocitos T/inmunología , Factor A de Crecimiento Endotelial Vascular/inmunología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Anciano , Anciano de 80 o más Años , Antígenos CD/genética , Antígenos CD/inmunología , Estudios de Casos y Controles , Quimiocina CCL2/genética , Retinopatía Diabética/genética , Retinopatía Diabética/patología , Retinopatía Diabética/cirugía , Femenino , Expresión Génica , Humanos , Inflamación , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Retina/inmunología , Retina/patología , Retina/cirugía , Perforaciones de la Retina/genética , Perforaciones de la Retina/patología , Linfocitos T/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Factor A de Crecimiento Endotelial Vascular/genética , Cirugía Vitreorretiniana/métodos , Cuerpo Vítreo/inmunología , Cuerpo Vítreo/patología , Cuerpo Vítreo/cirugíaAsunto(s)
Anticuerpos Antiidiotipos/inmunología , Membrana Epirretinal/inmunología , Inmunoglobulina G/inmunología , Retina/inmunología , Perforaciones de la Retina/inmunología , Humor Acuoso/inmunología , Humor Acuoso/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/metabolismo , Masculino , Persona de Mediana Edad , Prevalencia , Retina/metabolismo , Cuerpo Vítreo/inmunología , Cuerpo Vítreo/metabolismoRESUMEN
Objective To quantify T helper (Th)17 cells and determine interleukin (IL)-17A levels in peripheral blood mononuclear cell (PBMC) culture and vitreous fluid from patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy (DR). Methods Th17 cell frequency and IL-17A concentrations in PBMCs from 60 patients with T2DM with DR, 30 without DR and 30 sex- and age-matched healthy individuals were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. IL-17A levels in vitreous fluid from 31 eyes with proliferative DR and diabetic macular oedema (DR group) and 32 eyes with an epiretinal membrane and macular hole (control group) that underwent vitrectomy were also examined by ELISA. Results Compared with the control group, the proportion of Th17 cells and IL-17A concentrations in PBMCs were significantly increased in patients without DR but decreased in those with DR. IL-17A concentrations and Th17 cell frequency in PBMCs tended to decrease with DR severity and were negatively correlated with body mass index, T2DM duration and glycated haemoglobin. Additionally, vitreous fluid IL-17A levels were significantly elevated in patients with DR compared with those of the control group. Conclusions We conclude that disturbances in Th17 cells and IL-17A levels are possibly associated with DR.
Asunto(s)
Diabetes Mellitus Tipo 2/inmunología , Retinopatía Diabética/inmunología , Interleucina-17/genética , Leucocitos Mononucleares/inmunología , Células Th17/inmunología , Cuerpo Vítreo/inmunología , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/cirugía , Retinopatía Diabética/genética , Retinopatía Diabética/patología , Retinopatía Diabética/cirugía , Membrana Epirretinal/genética , Membrana Epirretinal/inmunología , Membrana Epirretinal/patología , Membrana Epirretinal/cirugía , Femenino , Expresión Génica , Hemoglobina Glucada/genética , Hemoglobina Glucada/inmunología , Humanos , Interleucina-17/inmunología , Leucocitos Mononucleares/patología , Edema Macular/genética , Edema Macular/inmunología , Edema Macular/patología , Edema Macular/cirugía , Masculino , Persona de Mediana Edad , Cultivo Primario de Células , Perforaciones de la Retina/genética , Perforaciones de la Retina/inmunología , Perforaciones de la Retina/patología , Perforaciones de la Retina/cirugía , Células Th17/patología , Vitrectomía , Cuerpo Vítreo/metabolismo , Cuerpo Vítreo/patología , Cuerpo Vítreo/cirugíaRESUMEN
PURPOSE: To evaluate the role of interleukin-6 (IL-6) in the inflammatory and proliferative stages of Eales' disease (ED) and to determine the influence of IL-6-174G/C polymorphism in the IL-6 and IL-6-regulated protein expression, as well as the development of ED. METHODS: One hundred and twenty-one patients diagnosed with ED, 223 matched healthy controls, and 16 control patients with macular holes were recruited from the eastern Indian population. Serum and vitreous levels of IL-6 and vascular endothelial growth factors (VEGF) were measured by enzyme-linked immunosorbent assay. Serum levels of high-sensitivity C-reactive protein (hsCRP) were measured by enzyme immunoassay. Subjects were genotyped for the IL-6-174G/C polymorphism (rs1800795) by a custom TaqMan single-nucleotide polymorphism (SNP) Genotyping Assays system. RESULTS: Serum IL-6 (p<0.0001), hsCRP (p<0.0001), and VEGF (p=0.0031) levels were significantly higher in the inflammatory stage of ED than in healthy controls. Serum IL-6 also significantly correlated with hsCRP (Spearman's correlation coefficient; r=0.4992, p=0.0009), but not with VEGF in this stage in ED patients. At the proliferative stage of ED, significantly higher levels of vitreous IL-6 (p=<0.0001) and VEGF (p=<0.0001) were found compared with the vitreous of patients with macular holes. A significant correlation was observed between vitreous IL-6 and VEGF in ED patients (Spearman's correlation coefficient; r=0.5834, p=0.0087). A statistically significant association was found between the -174GG genotype (p=0.006) and occurrence of ED. Mean serum and vitreous concentrations of IL-6 were also higher in the subjects with the GG genotype than in those with the GC or CC genotype in this population. CONCLUSIONS: IL-6 expression, regulated by the allelic distribution of -174 loci and the enhanced level of IL-6, modulates CRP and VEGF concentration depending respectively on the acute inflammatory stimulation at the initial stage and angiogenic stimulation at the advanced stage of ED.
Asunto(s)
Inflamación/genética , Interleucina-6/genética , Neovascularización Patológica/genética , Polimorfismo de Nucleótido Simple , Vasculitis Retiniana/genética , Cuerpo Vítreo/inmunología , Enfermedad Aguda , Adulto , Anciano , Proteína C-Reactiva/análisis , Proteína C-Reactiva/biosíntesis , Estudios de Casos y Controles , Dermatoglifia del ADN , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , India , Inflamación/complicaciones , Inflamación/epidemiología , Inflamación/inmunología , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/complicaciones , Neovascularización Patológica/epidemiología , Neovascularización Patológica/inmunología , Regiones Promotoras Genéticas , Perforaciones de la Retina/genética , Perforaciones de la Retina/inmunología , Vasculitis Retiniana/complicaciones , Vasculitis Retiniana/epidemiología , Vasculitis Retiniana/inmunología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/inmunología , Cuerpo Vítreo/químicaRESUMEN
The authors analyze the results of clinical and immunological examinations of patients with peripheral vitreo-chorioretinal dystrophies (PVCRD) and macular ruptures of the retina. No antibodies to S-AG were detected in the lacrimal fluid in 87.5% of patients with PVCRD without retinal defects. In patients with PVCRD with retinal defects antibodies to S-AG were detected in 70% of cases. These antibodies were absent in the patients with macular ruptures of the retina. In none of the patients were these antibodies detected in the blood serum. The levels of circulating immune complexes were normal in the patients PVCRD and increased in those with macular ruptures of the retina. These data permit a hypothesis on the development of local autoimmune reactions in PVCRD patients in response to the appearance of AG of the injured tissues.
Asunto(s)
Degeneración Retiniana/inmunología , Perforaciones de la Retina/inmunología , Adolescente , Adulto , Complejo Antígeno-Anticuerpo/análisis , Enfermedades de la Coroides/inmunología , Oftalmopatías/inmunología , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Lágrimas/inmunología , Cuerpo VítreoRESUMEN
Mononuclear phagocytes are considered pacemakers in the pathogenesis of proliferative vitreoretinopathy (PVR), but their precise biological origin in preretinal PVR traction membranes has remained obscure. This study presents a combined immunohistochemical protocol for the detection of microglial cells, which was applied to 37 membranes of patients with idiopathic and traumatic PVR and with proliferative diabetic retinopathy (PDR). Microglial cells may be labeled by staining for LN-1, ricinus communis agglutinin-(RCA)-1, vimentin, HLA-DR-II, and nucleoside diphosphatase, but are negative for Leu-M1, Leu-M3, EBM-11, von Willebrand factor, CD22, cytokeratin, and glial fibrillary acidic protein (GFAP). Significant proliferation of microglial cells was found in idiopathic PVR while classical macrophages were typical of traumatic PVR. Only rarely were microglial cells detected in PDR. These findings bring into question previous concepts of the pathobiology of idiopathic PVR and support the hypothesis of idiopathic PVR as a specific disease entity.