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PURPOSE: To describe a new insight into the Climate Droplet Keratopathy (CDK) pathophysiology and its major predisposing factors. METHOD: A literature search was undertaken on PubMed to compile papers published on CDK. The following is a focused opinion tempered by synthesis of current evidence, and research of the authors. RESULTS: CDK is a multifactorial rural disease common in regions with high incidence of pterygium, but not related to the type of climate or ozone concentrations. Although it has been thought that climate is the cause of this disease, recent investigations deny that and reveal that other environmental factors such as dietary intake, eye protection, oxidative stress, and ocular inflammatory pathways play an important role in the pathogenesis of CDK. CONCLUSION: Considering the negligible effect of climate, the present name " CDK" for this illness can be confusing for young ophthalmologists. Based on these remarks, it is imperative to start using an accurate name like "Environmental Corneal Degeneration (ECD)" that fits the most recent evidence related to its etiology.
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Enfermedades de la Córnea , Distrofias Hereditarias de la Córnea , Pterigion , Humanos , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/etiología , Pterigion/complicaciones , Estrés OxidativoRESUMEN
INTRODUCTION: The intestinal microbiota plays an important role in modulating host immune responses. Oral Toxoplasma gondii infection can promote intestinal inflammation in certain mice strains. The IDO-AhR axis may control tryptophan (Trp) metabolism constituting an important immune regulatory mechanism in inflammatory settings. AIMS: In the present study, we investigated the role of the intestinal microbiota on Trp metabolism during oral infection with T gondii. METHODS AND RESULTS: Mice were treated with antibiotics for four weeks and then infected with T gondii by gavage. Histopathology and immune responses were evaluated 8 days after infection. We found that depletion of intestinal microbiota by antibiotics contributed to resistance against T gondii infection and led to reduced expression of AhR on dendritic and Treg cells. Mice depleted of Gram-negative bacteria presented higher levels of systemic Trp, downregulation of AhR expression and increased resistance to infection whereas depletion of Gram-positive bacteria did not affect susceptibility or expression of AhR on immune cells. CONCLUSION: Our findings indicate that the intestinal microbiota can control Trp availability and provide a link between the AhR pathway and host-microbiota interaction in acute infection with T gondii.
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Microbioma Gastrointestinal/fisiología , Toxoplasmosis/metabolismo , Triptófano/metabolismo , Animales , Femenino , Inflamación/inmunología , Ratones , Ratones Endogámicos C57BL , Toxoplasma/inmunología , Toxoplasmosis/inmunologíaRESUMEN
BACKGROUND: Retinal tears complicating the course of a posterior vitreous detachment (PVD) may be unique or multiple, and when multiple they may occur simultaneously or subsequently at different moments in the evolution of a PVD. The purpose of our study was to analyze the prevalence of subsequent retinal tears (SRT) in patients with a PVD, and to identify possible risk factors for SRT. METHODS: One hundred and seventy six eyes in 165 consecutive patients that presented one or more retinal tears in the evolution of a symptomatic PVD, with a minimum follow-up of 12 months, were retrospectively evaluated. The primary outcome measure was to characterize the clinical features associated with SRT formation against those eyes with non-subsequent retinal tear (NSRT-retinal tear/s diagnosed at initial examination) formation. For that purpose, this cohort of patients was divided into two different groups: group 1 included eyes presenting one or multiple retinal tears only at initial examination (NSRT), and group 2 eyes that progressed to a further retinal tear/s (SRT) during follow-up. RESULTS: Group 1 comprised 154 eyes from 145 patients, 48.7% males and 51.3% females with a mean age of 56.9 ± 14.0 years (range = 15-89); 17.2% of patients had a previous retinal tear or retinal detachment in the fellow eye; mean number of retinal tears per eye 1.42 ± 0.8 (range = 1-5); 20.8% presented bilateral retinal tears; 59.1% were myopic eyes (p < 0.05). Group 2 comprised 22 eyes from 20 patients; mean age was 53.3 ± 13.6 years (range = 30-69); 63.6% were male (p = 0.13), and 7 patients (31.8%) had a history of SRT or retinal detachment in the fellow eye (p = 0.13). The mean number of retinal tears per eye was 1.36 ± 0.5 (range = 1-2); bilateral retinal tears were noted in 18.2% of eyes; 86.4% were myopic eyes (p = 0.01); 81.8% occurred within a 120 days-period following diagnosis of the first retinal tear. CONCLUSIONS: Multiple retinal tears may be diagnosed in the evolution of a PVD. SRT are most frequently observed in myopic patients, and are usually symptomatic. Follow-up must extend for at least 4 months after the initial symptoms.
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Miopía/complicaciones , Perforaciones de la Retina/epidemiología , Desprendimiento del Vítreo/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Perforaciones de la Retina/etiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Climatic droplet keratopathy (CDK) is an acquired degenerative disease predominantly affecting males over 40 years old. It results in progressive corneal opacities usually affecting both eyes. CDK is multifactorial and its etiology remains unknown. Our recent findings are consistent with CDK pathology being driven by environmental factors with oxidative stress playing an important role (e.g.,, contributing to lipid peroxidation) rather than climate factors. The changes in corneal lipid composition affected by environmental factors remain understudied. The purpose of this study was to systematically investigate phospholipids profile (phosphatidylcholine [PC] and phosphatidylserine [PS]) in corneas from CDK patients using tandem mass spectrometry. Samples from CDK areas and from non-affected areas were obtained from patients diagnosed with CDK who underwent cataract surgery, were subjected to lipid extraction using a modified Bligh and Dyer method; protein concentrations were determined using the Bradford's method. Lipids were identified and subjected to ratiometric quantification using TSQ Quantum Access Max triple quadrupole mass spectrometer, using appropriate class specific lipid standards. All phospholipid classes showed lower total amounts in affected areas compared to control areas from CDK's corneas. Comparative profiles of two phospholipid classes (PC, PS) between CDK areas and control areas showed several common species between them. We also found a few unique lipids that were absent in CDK areas compared to controls and vice versa. Lower amount of phospholipids in CDK areas compared to control areas could be attributed to the lipid peroxidation in the affected corneal regions as a consequence of increased oxidative stress. J. Cell. Biochem. 118: 3920-3931, 2017. © 2017 Wiley Periodicals, Inc.
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Córnea/metabolismo , Enfermedades de la Córnea/metabolismo , Estrés Oxidativo , Fosfolípidos/metabolismo , Córnea/patología , Enfermedades de la Córnea/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Conjunctival amyloidosis is a very rare condition, generally unilateral, and presents mostly as an isolated condition without systemic compromise. Our purpose is to present a new case of systemic amyloidosis with a bilateral conjunctival involvement. CASE PRESENTATION: A 66-years-old caucasian female complaining of conjunctival hemorrhage and chemosis in both eyes for the last five years had been discontinuously treated with topical antibiotics and corticosteroids without any evident improvement. She presented with a pink-yellow infiltration in the inferior conjunctiva of both eyes. Conjunctival biopsy under optical microscopy revealed amyloid deposit, confirmed by Congo red staining. Mucosal biopsy from esophagus and rectus confirmed amyloidosis by Congo red stain. Immunohistochemistry of bone marrow biopsy showed an increased number of plasma cells and an over-expression of light chain kappa subunit. She was treated with corticosteroids and lubrication with an improvement of symptoms. Ocular lesions remained stable after a follow-up of 3 years. CONCLUSIONS: Conjunctival amyloidosis is a rare entity that may be overlooked, and should be differentiated from chronic conjunctivitis and conjunctival malignancies. Although it presents most frequently as a local process, a systemic involvement should always be ruled out.
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Amiloidosis/complicaciones , Enfermedades de la Conjuntiva/complicaciones , Anciano , Amiloidosis/diagnóstico , Amiloidosis/metabolismo , Células de la Médula Ósea/metabolismo , Enfermedades de la Conjuntiva/diagnóstico , Enfermedades de la Conjuntiva/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Sindecano-1/metabolismoRESUMEN
Climatic droplet keratopathy (CDK) is an acquired and potentially handicapping cornea degenerative disease that is highly prevalent in certain rural communities around the world. It predominantly affects males over their forties. It has many other names such as Bietti's band-shaped nodular dystrophy, Labrador keratopathy, spheroidal degeneration, chronic actinic keratopathy, oil droplet degeneration, elastoid degeneration and keratinoid corneal degeneration. CDK is characterized by the haziness and opalescence of the cornea's most anterior layers which go through three stages with increasing severity. Globular deposits of different sizes may be histopathologically observed under the corneal epithelium by means of light and electron microscopy. The coalescence and increased volume of these spherules may cause the disruption of Bowman's membrane and the elevation and thinning of the corneal epithelium. The exact aetiology and pathogenesis of CDK are unknown, but they are possibly multifactorial. The only treatment in CDK advanced cases is a corneal transplantation, which in different impoverished regions of the world is not an available option. Many years ago, the clinical and histological aspects of this disease were described in several articles. This review highlights new scientific evidence of the expanding knowledge on CDK's pathogenesis which will open the prospect for new therapeutic interventions.
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Córnea/patología , Distrofias Hereditarias de la Córnea/patología , Animales , Ácido Ascórbico/uso terapéutico , Distrofias Hereditarias de la Córnea/etiología , Distrofias Hereditarias de la Córnea/genética , Distrofias Hereditarias de la Córnea/terapia , Trasplante de Córnea , Modelos Animales de Enfermedad , Humanos , Factores SexualesRESUMEN
UNLABELLED: We report a case of Alternaria keratitis and hypopyon following clear-corneal cataract surgery. A 66-year-old woman presented with a painful red left eye several months after uneventful self-sealing clear-corneal phacoemulsification that was unresponsive to prolonged treatment with topical/oral quinolones and topical corticosteroids. A full-thickness stromal white dense infiltrate in the area of the intrastromal tunnel incision and a 2.0 mm hypopyon were observed. Culture from corneal scrapings revealed Alternaria species. Treatment included topical and subconjunctival injections of amphotericin-B (5 mg/mL) and 200 mg of oral ketoconazole. Complete resolution of the corneal infiltration and hypopyon was observed after 30 days of treatment, with no recurrence during 6 years of follow-up. To our knowledge, this is the first report of Alternaria species keratitis complicating self-sealing clear-corneal cataract surgery. Topical and subconjunctival injections of amphotericin-B and oral ketoconazole were effective in resolving the corneal abscess and anterior chamber inflammatory reaction. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
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Absceso/microbiología , Alternaria/aislamiento & purificación , Alternariosis/microbiología , Córnea/cirugía , Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/microbiología , Facoemulsificación , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Administración Oral , Anciano , Alternariosis/diagnóstico , Alternariosis/tratamiento farmacológico , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Córnea/efectos de los fármacos , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Femenino , Humanos , Inyecciones Intraoculares , Cetoconazol/uso terapéutico , Implantación de Lentes Intraoculares , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To determine whether the incidence of and susceptibility to climatic droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal disease, is influenced by the genetic background of the individuals who exhibit the disorder. METHODS: To determine whether the disease expression was influenced by the genetic ancestry of CDK cases in native Mapuche of the northwest area of Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient) population, while 24 were part of the control group. The analysis revealed the maternal and paternal lineages that were present in the two study groups. RESULTS: This analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. There was no significant difference in the frequencies of mtDNA haplogroups between the CDK patient and control groups. Although the Y-chromosome data revealed differences in specific haplogroup frequencies between these two groups, there was no statistically significant relationship between individual paternal genetic backgrounds and the incidence or stage of disease. CONCLUSIONS: These results indicate a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears to play less of a role in CDK expression than for other complex diseases linked to bioenergetic processes. However, further analysis of the mtDNA genome sequence and other genes involved in corneal function may reveal the more precise role that mitochondria play in the expression of CDK.
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Enfermedades de la Córnea/etnología , Enfermedades de la Córnea/genética , Predisposición Genética a la Enfermedad , Adulto , Argentina , Estudios de Casos y Controles , Cromosomas Humanos Y/genética , Enfermedades de la Córnea/epidemiología , ADN Mitocondrial/genética , Femenino , Variación Genética , Genética de Población , Haplotipos , Humanos , Incidencia , Indígenas Sudamericanos , Masculino , Lágrimas/químicaRESUMEN
AIMS: To assess the impact of different oxygenation policies on the rate and severity of retinopathy of prematurity (ROP). METHODS: Between January 2003 and December 2006, infants of 1500 g birthweight (BW) or less and/or 32 weeks gestational age (GA) or less, and larger, more mature infants with risk factors for ROP were examined through three different time periods: period 1: high target oxygen saturation levels (88-96%) and treatment at threshold ROP; period 2: low target oxygen saturation levels (83-93%) and treatment at threshold ROP; period 3: low target oxygen saturation and treatment at type 1 ROP. RESULTS: Type 1 ROP was detected more frequently in babies of 32 weeks GA or less (50/365, 13.7%) than in more mature babies (15/1167, 1.3%; p<0.001). The rate of type 1 ROP in period 1 was 6.9%; period 2, 3.6% and period 3, 1.8%. Rates of stage 3 ROP declined over time in both BW/GA groups (from 9.0% to 4.1% to 2.0%) as did rates of plus disease (from 7.5% to 3.6% to 1.8%). Mean BW and GA declined from period 1 to period 3, and death rates remained unchanged. 74.4% of babies received all the examinations required; 48.1% of treatments were undertaken after discharge from the neonatal unit. CONCLUSIONS: Lower target oxygen saturation was associated with a lower rate of severe ROP without increasing mortality, and changed the characteristics of affected babies. Screening criteria need to remain wide enough to identify all babies at risk of ROP needing treatment.
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Unidades de Cuidado Intensivo Neonatal , Consumo de Oxígeno/fisiología , Terapia por Inhalación de Oxígeno/normas , Guías de Práctica Clínica como Asunto , Retinopatía de la Prematuridad/terapia , Argentina/epidemiología , Estudios de Seguimiento , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Retinopatía de la Prematuridad/metabolismo , Retinopatía de la Prematuridad/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendenciasRESUMEN
PURPOSE: To determine levels of Peptidyl arginine deiminase 2 (PAD2) and its product protein-bound citrulline in cadaver eyes that suffered from normal tension glaucoma (NTG) compared to primary open angle glaucoma (POAG), and controls. METHODS: Western analysis, ELISA, and immunohistochemical analysis were performed with human tissues. RESULTS: We report over expression of PAD2 and higher levels of its product protein-bound citrulline in the optic nerve of normal tension glaucoma patients (NTG). CONCLUSIONS: This is the first report demonstrating that like in POAG, NTG also possesses elevated levels of both PAD2 and protein-bound citrulline.
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Glaucoma/enzimología , Glaucoma/patología , Hidrolasas/metabolismo , Nervio Óptico/enzimología , Nervio Óptico/patología , Anciano , Anciano de 80 o más Años , Citrulina/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Arginina Deiminasa Proteína-Tipo 2 , Desiminasas de la Arginina Proteica , Donantes de TejidosRESUMEN
OBJECTIVE: To describe the functional and structural characteristics of the cornea in healthy Guinea pigs. ANIMALS STUDIED: Healthy male and female pigmented and albino Guinea pigs (Caviaporcellus) aged 3-5 months old were used. PROCEDURES: The animals' corneas underwent different in vivo studies including: slit-lamp biomicroscopy, fluorescein staining (FS), break-up time test (BUT), confocal microscopy and pachymetry. The corneas were also studied histopathologically with light microscopy, immunohistochemistry and transmission electron microscopy. RESULTS: No significant differences were found between pigmented and albino animals, male and female, OD and OS in any study performed. The differences on corneal thickness values were not significant among central (227.85 +/- 14.09 microm) and upper and temporal peripheral regions (226.60 +/- 12.50 and 225.70 +/- 14.40 microm, respectively). All histological studies performed permitted identification and precise description of the different corneal structures in Guinea pigs: the stratified epithelium (45.52 +/- 5.26 microm), Bowman's layer (2.23 +/- 0.38 microm), stroma (163.69 +/- 4.90 microm), Descemet's membrane (3.96 +/- 0.46 microm) and the endothelium (5.09 +/- 0.71 microm). Combining results from all eyes mean and SD from corneal BUT values was 4.98 +/- 1.67 s. Corneas often showed discrete superficial erosions being the FS positive in both eyes from all the animals. CONCLUSION: This study provides a detailed in vivo and postfixed histological description of the Guinea pig's cornea and information about the physiological tests.
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Córnea/anatomía & histología , Córnea/fisiología , Cobayas/anatomía & histología , Cobayas/fisiología , Animales , Femenino , Masculino , MicroscopíaRESUMEN
PURPOSE: To present external eye findings and the observation of iris atrophy in patients with climatic droplet keratopathy (CDK). METHODS: Twenty-three patients with CDK and 13 controls living in a semideserted plain of the Argentine Patagonia were studied. Besides a comprehensive eye examination, Cochet-Bonnet aesthesiometry, Schirmer II test, breakup time (BUT), and surface staining were performed. According to corneal findings, eyes were grouped as grade 1 (confluent translucent microdroplets localized in the limbic region of the horizontal quadrants); grade 2 (band-shaped subepithelial haziness compromising the central cornea); and grade 3 (previously described lesions with yellow subepithelial droplets). Results were analyzed with the Fisher, Mann-Whitney, and Spearman tests, which were considered significant at P < 0.05. RESULTS: Nineteen of 23 patients with CDK had bilateral disease, which was asymmetric in 2 of them. Sixteen eyes had grade 1, 21 eyes had grade 2, and 5 eyes had grade 3 disease. Aesthesiometry showed that the more advanced the disease, the more profound the corneal hypoesthesia (P = 0.0008). BUT and ocular surface staining significantly differed between eyes with grade 3 and grade 1, grade 3 and grade 2, and grade 3 and controls. In 38.09% of eyes with CDK and in none of the controls, sectorial depigmentation and atrophy of the inferior iris were observed. CONCLUSIONS: A severe decrease of corneal sensitivity was observed in advanced stages of CDK. Some degree of dry eye was present in most patients, but severe disease was infrequent at any stage of CDK. Inferior iris depigmentation and atrophy was frequently observed among patients with CDK.
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Córnea/patología , Enfermedades de la Córnea/complicaciones , Hipoestesia/complicaciones , Iris/patología , Anciano , Anciano de 80 o más Años , Argentina , Atrofia/complicaciones , Atrofia/diagnóstico , Enfermedades de la Córnea/diagnóstico , Clima Desértico , Técnicas de Diagnóstico Oftalmológico , Femenino , Humanos , Hipoestesia/diagnóstico , Masculino , Persona de Mediana Edad , Lágrimas/metabolismo , Tacto , Agudeza VisualRESUMEN
La función fisiológica del sistema inmune es la defensa del hospedador frente a agentes infecciosos. Esta respuesta es en primer termino innata, es la primera línea de defensa, mediada por células y moléculas cuyo objetivo es eliminar al gente infeccioso. Luego le sigue una respuesta adaptativa la cual se genera una vez que el agente agresor haya penetrado en los tejidos del hospedador, por esto este tipo de respuesta es altamente específica. Esta respuesta adaptativa consiste en mecanismos humoral es mediados por linfocitos B y sus anticuerpos específicos secretados y mecanismos mediados por células donde los efectores son los linfocitos T. La respuesta inmune consiste en una secuencia de fase entre las cuales se encuentran: reconocimiento específico de antígenos por los linfocitos, activación y proliferación linfocitaria, diferenciación a célula efectora y célula de memoria, eliminación del agente agresor, declinación de la respuesta inmune, generación de memoria inmunológica a largo plazo.
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Sistema InmunológicoRESUMEN
Intraocular inflammatory diseases are a common cause of severe visual impairment and blindness. In this study, we investigated the immunoregulatory role of galectin-1 (Gal-1), an endogenous lectin found at sites of T cell activation and immune privilege, in experimental autoimmune uveitis (EAU), a Th1-mediated model of retinal disease. Treatment with rGal-1 either early or late during the course of interphotoreceptor retinoid-binding protein-induced EAU was sufficient to suppress ocular pathology, inhibit leukocyte infiltration, and counteract pathogenic Th1 cells. Administration of rGal-1 at the early or late phases of EAU ameliorated disease by skewing the uveitogenic response toward nonpathogenic Th2 or T regulatory-mediated anti-inflammatory responses. Consistently, adoptive transfer of CD4(+) regulatory T cells obtained from rGal-1-treated mice prevented the development of active EAU in syngeneic recipients. In addition, increased levels of apoptosis were detected in lymph nodes from mice treated with rGal-1 during the efferent phase of the disease. Our results underscore the ability of Gal-1 to counteract Th1-mediated responses through different, but potentially overlapping anti-inflammatory mechanisms and suggest a possible therapeutic use of this protein for the treatment of human uveitic diseases of autoimmune etiology.
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Enfermedades Autoinmunes/prevención & control , Galectina 1/fisiología , Inmunosupresores/administración & dosificación , Mediadores de Inflamación/fisiología , Retinitis/prevención & control , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Uveítis/prevención & control , Traslado Adoptivo , Animales , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/patología , Galectina 1/administración & dosificación , Mediadores de Inflamación/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/administración & dosificación , Retinitis/inmunología , Retinitis/patología , Linfocitos T Reguladores/trasplante , Células Th2/trasplante , Uveítis/inmunología , Uveítis/patologíaRESUMEN
PURPOSE: To present the findings of climatic droplet keratopathy (CDK) that affects people of a rural area of the Argentine Patagonia. DESIGN: Observational case series. METHODS: Five hundred seventy-seven individuals who live in settlements and villages in an inland area of the northwest Patagonia region in Argentina received a complete eye examination. RESULTS: The mean age was 36.02 years (r = 1.5 months to 89 years); 55.63% of the patients were female. The mean age of the 7.62% of the patients who had typical CDK was 65.31 years (r = 42 to 89 years); 86.36% of the patients were male. Of 66 eyes in 35 patients with CDK, 35 eyes had peripheral haziness (grade 1); 23 eyes had a band-shaped haziness (grade 2), and 8 eyes had the aggregate of yellow subepithelial droplets (grade 3). Pinguecula, pterygium, cataract, and pseudoexfoliation were frequent findings among patients with CDK. CONCLUSION: CDK is not infrequent among male adults in this area of the Argentine Patagonia and may be severely handicapping.
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Enfermedades de la Córnea/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Argentina/epidemiología , Niño , Preescolar , Córnea/patología , Enfermedades de la Córnea/diagnóstico , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Distribución por SexoRESUMEN
PURPOSE: Recruitment of lymphocytes into the retina and to the vitreous during the development of experimental autoimmune uveitis (EAU) is governed by factors such as the state of activation of inflammatory cells and the repertoire of adhesion molecules expressed by the local vascular endothelia. alpha4 Integrins and their receptors play an important role during homing of cells to the inflammatory site. In the present study, the effect of alpha4-integrin inhibitor on the development of EAU was investigated. METHODS: EAU was induced either by immunizing B10.RIII mice with the 161-180 peptide or by adoptive transfer of interphotoreceptor retinoid-binding protein (IRBP)-specific uveitogenic T cells. Animals were treated with an active peptide inhibitor (alpha4-api) or a peptide control at different time points after induction of disease. EAU was evaluated by histology 21 to 49 days after immunization. Antigen-specific cell proliferation was evaluated by thymidine incorporation. Cytokine synthesis in culture supernatants and anti-IRBP-specific serum IgG1 and IgG2a were evaluated by ELISA. Delayed-type hypersensitivity was evaluated by ear challenge 2 days before the termination of the experiment. RESULTS: Treatment with alpha4-api had a significant ameliorating effect on EAU. The anti-IRBP antibody response and cellular proliferation were not affected by the treatment, whereas delayed-type hypersensitivity was significantly diminished. Cytokine synthesis was not changed by treatment, except for a decrease in IL-10 levels. CONCLUSIONS: The results show that small-molecule inhibitors of alpha4-integrins can act therapeutically in EAU, possibly by interfering with cell adhesion events involved in the development of the disease.
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Enfermedades Autoinmunes/prevención & control , Integrina alfa4beta1/antagonistas & inhibidores , Oligopéptidos/uso terapéutico , Uveítis Posterior/prevención & control , Traslado Adoptivo , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Citocinas/sangre , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Proteínas del Ojo/inmunología , Hipersensibilidad Tardía/inmunología , Hipersensibilidad Tardía/prevención & control , Inmunoglobulina G/sangre , Activación de Linfocitos , Ratones , Fragmentos de Péptidos/inmunología , Proteínas de Unión al Retinol/inmunología , Linfocitos T/inmunología , Uveítis Posterior/inmunología , Uveítis Posterior/patologíaRESUMEN
BACKGROUND: The efficacy and safety of ketotifen eye drop treatment in allergic conjunctivitis (AC) management is perfectly known by several studies, but the mechanism of action at the biochemical levels is poorly understood so we decided to perform an open, uncontrolled study in order to investigate the effect of the topical administration of ketotifen fumarate 0.05% on biochemical markers of inflammation on conjunctival cells in patients with AC. METHODS: Nineteen patients with symptoms and signs of AC (itching, discharge, burning, redness, increase in the watery discharge, swelling and follicles) and with a history of allergy were prescribed with two daily instillation of one drop of eyewash ketotifen fumarate 0,05% in both eyes during thirty days. They were studied by measuring clinical and immunologic parameters. RESULTS: Ketotifen fumarate treatment significantly reduced the total symptoms and signs score for each patient as well as each symptoms and signs at all time points compared with day 0 (p < 0.0001 and p < 0.016, respectively). Although the percentage of HLA-DR+ epithelial cells diminished only in 58% of patients, the numbers of CD29+ and eotaxin+ epithelial cells dropped significantly in 68% and 73 % of them (p < 0.0062 and <0.0082, respectively) as a consequence of the treatment. In 9 out of 19 patients a simultaneous decrease in the percentage of epithelial cells positive for CD29 and eotaxin was observed. CONCLUSION: Ketotifen besides the well-known effect in reducing signs and symptoms of AC significantly diminished production of eotaxin and expression of CD29 by epithelial cells in patients with seasonal AC.
Asunto(s)
Quimiocinas CC/metabolismo , Conjuntivitis Alérgica/tratamiento farmacológico , Antígenos HLA-DR/metabolismo , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Integrina beta1/metabolismo , Cetotifen/uso terapéutico , Administración Tópica , Adolescente , Adulto , Biomarcadores/análisis , Quimiocina CCL11 , Factores Quimiotácticos Eosinófilos/metabolismo , Niño , Conjuntiva/efectos de los fármacos , Conjuntiva/metabolismo , Conjuntivitis Alérgica/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Humanos , Cetotifen/administración & dosificación , Masculino , Persona de Mediana Edad , Soluciones OftálmicasRESUMEN
Antecedentes: si bien la dermatitis alérgica por contacto (DAC) es una dermatosis humana frecuente, no todos los mecanismos involucrados en su patogenia han sido dilucidados. Objetivo: estudiar la cinética de expresión de CCL2, CS-1 fibronectina y CCL17 en biopsias de reacciones provocadas por pruebas de parches. Diseño: diez pacientes diagnosticados con DAC fueron desafiados en la espalda con antígenos inductores e irrelevantes. A las 2, 10 y 48 horas se observaron las respuestas macroscópicas y se obtuvieron biopsias, las cuales fueron procesadas para realizar estudios histológicos, inmunohistoquímicos y de hibridización in situ. Resultados: todos los individuos presentaron a las 48 horas una respuesta clínica positiva y un infiltrado celular mononuclear perivascular, el cual no fue observado en los controles negativos. ARNm para CCL2 fue encontrado solamente en sitios positivos a las 10 y 48 horas. Los endotelios inflamados expresaron CS-1 fibronectina y CCL17. El número de células CD+ y CD68+ aumentó significativamente con el tiempo en los parches positivos (p<0,0001). En éstos mismos sitios las células infiltrantes CCR5+ y CXCR3+, pero no las CCR3+ también incrementaron significativamente entre las 2 y 10 horas (p<0,03), y a las 48 horas, el porcentaje de células CCR5+ y CXCR3+ a las 10 y 48 horas (rs=0,9; p=0,0007). Conclusión: éste estudio demuestra por primera vez la producción de CCL2 y CS-1 fibronectina en la piel de pacientes con DAC en respuesta al desafío antigénico específico (AU)
Asunto(s)
Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Femenino , Dermatitis Alérgica por Contacto/inmunología , Queratinocitos , Quimiocinas , Fibronectinas , Dermatitis Alérgica por Contacto/patología , Dermatitis Alérgica por Contacto/diagnóstico , Pruebas Cutáneas , Citocinas , Níquel/efectos adversos , Fenilendiaminas/efectos adversos , Cobalto/efectos adversos , Timerosal/efectos adversos , Perfumes/efectos adversos , InmunohistoquímicaRESUMEN
Antecedentes: si bien la dermatitis alérgica por contacto (DAC) es una dermatosis humana frecuente, no todos los mecanismos involucrados en su patogenia han sido dilucidados. Objetivo: estudiar la cinética de expresión de CCL2, CS-1 fibronectina y CCL17 en biopsias de reacciones provocadas por pruebas de parches. Diseño: diez pacientes diagnosticados con DAC fueron desafiados en la espalda con antígenos inductores e irrelevantes. A las 2, 10 y 48 horas se observaron las respuestas macroscópicas y se obtuvieron biopsias, las cuales fueron procesadas para realizar estudios histológicos, inmunohistoquímicos y de hibridización in situ. Resultados: todos los individuos presentaron a las 48 horas una respuesta clínica positiva y un infiltrado celular mononuclear perivascular, el cual no fue observado en los controles negativos. ARNm para CCL2 fue encontrado solamente en sitios positivos a las 10 y 48 horas. Los endotelios inflamados expresaron CS-1 fibronectina y CCL17. El número de células CD+ y CD68+ aumentó significativamente con el tiempo en los parches positivos (p<0,0001). En éstos mismos sitios las células infiltrantes CCR5+ y CXCR3+, pero no las CCR3+ también incrementaron significativamente entre las 2 y 10 horas (p<0,03), y a las 48 horas, el porcentaje de células CCR5+ y CXCR3+ a las 10 y 48 horas (rs=0,9; p=0,0007). Conclusión: éste estudio demuestra por primera vez la producción de CCL2 y CS-1 fibronectina en la piel de pacientes con DAC en respuesta al desafío antigénico específico