RESUMO
PURPOSE: To determine the relationship between the levels of intraocular inflammatory cytokines and polypoidal choroidal vasculopathy (PCV). METHODS: Prospective cohort study. Sixty-two patients with PCV and 36 control subjects were studied. The levels of cytokines, chemokines, and growth factors in the aqueous humor samples from PCV patients and control subjects were assessed for significant associations with PCV. Logistic regression analysis was used to compute the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles. RESULTS: In PCV patients, IL-4, IL-10, and IL-23 were significantly higher than in the controls. Logistic analyses showed a significantly high risk for IL-23 (OR for the highest quartile compared with the lowest quartile: 16.3; 95% CI: 3.5-75.2), VEGF (5.7; 1.2-26.1), and IL-4 (4.0; 1.3-12.7). IL-10 and IL-4, but not IL-23, were significantly correlated with the VEGF levels in PCV patients (IL-10: ρ = 0.477, IL-4: ρ = 0.281). The elevated levels of IL-5, IL-10, IL-4, IL-23, and IL-1α were found to be significantly associated with exudative lesion(s) in the fluorescein angiograms. CONCLUSIONS: The significant associations between elevated levels of IL-23 with PCV and its activity strongly suggest an involvement of inflammatory processes in the etiology of PCV, presumably independent of VEGF. (www.umin.ac.jp/ctr number, UMIN000003854.).
Assuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/metabolismo , Interleucina-23/metabolismo , Idoso , Biomarcadores/metabolismo , Corioide/metabolismo , Neovascularização de Coroide/patologia , Ensaio de Imunoadsorção Enzimática , Angiofluoresceinografia , Fundo de Olho , Humanos , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: To characterize the differential expression of intraocular inflammatory cytokines in eyes with branch retinal vein occlusion (BRVO) and to assess their roles as prognostic determinants of BRVO. METHODS: A prospective cohort study of 38 eyes with BRVO. Aqueous humor samples were collected just before the intravitreal injection of bevacizumab and were assessed for 18 cytokines, chemokines, and growth factors. For control, aqueous humor was collected from 28 eyes before cataract surgery. RESULTS: In the aqueous of eyes with BRVO, the IL-23, IL-8, IL-6, IL-15, IL-12, and IL-17 levels were significantly higher than that in control eyes. Pretreatment visual acuity was significantly correlated with the concentrations of IL-8, IL-10, IL-2, IL-1ß, IL-5, IL-6, IL-23, IL-4, MCP-1, IL-1α, IL-12, IL-13, IFN-γ, and IL-15. The pretreatment nonperfused area (NPA) was significantly correlated with the concentrations of IL-8, IL-2, MCP-1, and IL-6. Logistic regression analyses revealed significant associations between the BRVO and the concentrations of IL-8, IL-23, IL-12, IL-15, IL-10, IL-1ß, and IL-13. IL-8 had the highest odds ratio (OR) and was significantly associated with NPA, central retinal thickness (CRT), and visual acuity. Bevacizumab treatment significantly improved visual acuity and CRT after 1 month. Refractoriness to bevacizumab (defined as CRT recovery 1 month after treatment by <90%) was significantly associated with the IL-12 level. CONCLUSIONS: Of the induced cytokines in eyes with BRVO, IL-8 was the most significantly associated with the disease parameters of BRVO. IL-12 is most likely a factor that blocks the effect of bevacizumab treatment. (www.umin.ac.jp/ctr number, UMIN000003854.).
Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Humor Aquoso/metabolismo , Citocinas/metabolismo , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/metabolismo , Idoso , Anticorpos Monoclonais Humanizados , Bevacizumab , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Análise Multivariada , Razão de Chances , Oftalmoscopia , Estudos Prospectivos , Oclusão da Veia Retiniana/diagnóstico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
Angiogenesis is controlled by a balance between stimulators and inhibitors. We propose that the balance, as well as the general sensitivity of the endothelium to these factors, varies from individual to individual. Indeed, we have found that individual mouse strains have dramatically different responses to growth factor-induced neovascularization. Quantitative trait loci (QTLs), which influence the extent of corneal angiogenesis induced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), were previously identified by our laboratory. To investigate the genetic contribution to choroidal neovascularization (CNV), a leading cause of blindness, we have undertaken a similar mapping approach to identify QTLs that influence laser-induced CNV in the BXD series of recombinant inbred mouse strains. Composite interval mapping identified new angiogenic QTLs on chromosomes 2 and 19, in addition to confirming our previous corneal neovascularization QTLs of AngVq1 and AngFq2. The new QTLs are named AngCNVq1 and AngCNVq2. The newly mapped regions contain several candidate genes involved in the angiogenic process, including thrombospondin 1, delta-like 4, BclII modifying factor, phospholipase C, beta 2, adrenergic receptor, beta 1, actin-binding LIM protein 1 and colony stimulating factor 2 receptor, alpha. Differences in these regions may control individual susceptibility to CNV.
Assuntos
Neovascularização de Coroide/genética , Lasers/efeitos adversos , Locos de Características Quantitativas/genética , Animais , Mapeamento Cromossômico , Cromossomos , Genes , Predisposição Genética para Doença , Camundongos , Camundongos Endogâmicos , Neovascularização Patológica/genéticaRESUMO
We evaluated the efficacy of systemic 2-methoxyestradiol (2ME2) in a laser-induced murine model of choroidal neovascularization (CNV). C57BL/6J mice (8-week-old males) were used in this study and divided into four groups. After laser treatment, daily oral treatment with vehicle control, and 30, 50, and 75 mg/kg of 2ME2 was started. Two weeks after laser treatment, digital images of CNV were obtained from fluorescein isothiocyanate-dextran (FITC-dextran) angiography and choroidal flat mount after FITC-dextran perfusion. These images were quantified by NIH image software. Analysis of images from both FITC-dextran angiography and choroidal flat mount with FITC-dextran perfusion demonstrated that the 2ME2 treated groups showed a statistically significant, dose-dependent decrease in CNV. No toxicity or weight loss was observed during the treatment. Significant antiangiogenic effects of oral 2ME2 on laser induced CNV were observed. Since 2ME2 (Panzem) has demonstrated good safety in phase I/II trials for cancer, it has the potential to be used as a novel oral treatment for age-related macular degeneration.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Estradiol/análogos & derivados , 2-Metoxiestradiol , Administração Oral , Animais , Corioide/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Angiofluoresceinografia/métodos , Processamento de Imagem Assistida por Computador/métodos , Fotocoagulação a Laser/métodos , Degeneração Macular/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Neuroprotective effects of 6-formylpterin (6FP) on transient retinal ischemia-reperfusion injury were evaluated in rats by means of counting the number of retinal ganglion cells, measuring the thicknesses of the inner plexiform and inner nuclear layers, and by immunohistochemical detection of apoptotic cells in the retina. Sixty-one Sprague-Dawley rats (12 weeks, male, 295-330 g) were subjected to transient retinal ischemia-reperfusion by elevated intra-ocular pressure (80 mmHg for 60 min). Intraperitoneal injection of 6FP (3.8 mg/kg) was performed before or after ischemia. The retina was histologically better preserved in rats with 6FP treatment than without 6FP treatment. 6FP showed more strong neuroprotective effects when it was administered before ischemia. The number of single-stranded DNA-positive cells in the retina also decreased remarkably in rats with 6FP treatment, especially when administered before ischemia. These results suggest that 6FP protects retinal neurons from transient ischemia-reperfusion injury, at least in part by inhibiting apoptotic cell death.
Assuntos
Fármacos Neuroprotetores/farmacologia , Pterinas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Animais , Apoptose , Modelos Animais de Doenças , Imuno-Histoquímica , Injeções Intraperitoneais , Fármacos Neuroprotetores/administração & dosagem , Pterinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Deep-seated gliomas, including thalamic gliomas, have a poor prognosis because of difficulty of accessibility for surgery. In addition, an infiltrative pattern of the tumor is related to a poor prognosis. In this study, the infiltrative/invasive profile of the proliferating tumor cells of a right thalamic glioma was evaluated in an autopsied brain. A 71-year-old man died from extensive infiltration of a right thalamic glioma. The distribution of the proliferating tumor cells at the right thalamic tumor level was represented by the topographic map of MIB-1 labeling indices (LI) on the whole-brain coronal slice, and this map was analyzed with pathological findings and postmortem T2-weighted magnetic resonance imaging (MRI). The highest MIB-1 LI was 24% for the whole autopsy brain at the thalamic tumor level, whereas the MIB-1 LI was 21% for the biopsy sample of the right thalamic glioma. Because this patient survived only 9 months after diagnosis of the tumor as anaplastic astrocytoma, it was confirmed that 21% MIB-1 LI of the biopsy sample was relevant to his prognosis. The topographic map of MIB-1 LI showed that the proliferating tumor cells of the right thalamic glioma invaded the ventricular walls and the contralateral thalamus by the periventricular route, but there was no exophytic extension to the cortex. In conclusion, topographic analysis of the proliferative potential detected by MIB-1 immunostaining provides information on the growth pattern of human glioma.