RESUMEN
Several studies have reported the efficacy of traditional Chinese medicine (TCM) for central serous chorioretinopathy (CSC), while some ophthalmologists are concerned that TCM may be a risk factor for CSC as some chinese herbs contain hormonal ingredients. This study aimed to evaluate the efficacy and safety of TCM in treating patients with CSC. Randomized controlled trials (RCTs) and observational studies of TCM for CSC were searched up to July 10, 2023 on the following biological databases without language and publication time restrictions: PubMed, Ovid Medline, Embase, Cochrane Library, The Chinese National Knowledge Infrastructure Database (CNKI), Technology Periodical Database (VIP), Wanfang, and Chinese Biomedical Literature Service System (SinoMed). Review Manager V.5.4.1 and Stata 14 software were used for data analysis. Finally, thirty-eight studies were finally included including 23 RCTs and 15 cohort studies. The meta-analysis showed that compared with the routine treatment alone, the combination of TCM can not only reduce the recurrence rate (OR = 0.29, 95% CI: 0.21,0.40; I2 = 0%) and central retinal thickness (CRT) (MD = - 35.63, 95% CI: - 45.96,-25.30; I2 = 89%) of CSC, but improve patients' best corrected visual acuity (BCVA) (SMD = 0.86, 95% CI: 0.62,1.11; I2 = 77%); additionally, it has no obvious side effects compared with routine treatment (OR = 0.72, 95% CI: 0.39,1.34; I2 = 10%). Overall, this study shows that the use of TCM does not increase the risk of CSC recurrence; on the contrary, the combination of TCM may reduce the recurrence of CSC and improve BCVA and CRT in patients with CSC compared with conventional treatment.
Asunto(s)
Coriorretinopatía Serosa Central , Medicina Tradicional China , Coriorretinopatía Serosa Central/tratamiento farmacológico , Humanos , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Agudeza Visual/efectos de los fármacosRESUMEN
OBJECTIVE: To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy. METHODS: A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups. RESULTS: Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05). CONCLUSION: On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.
Asunto(s)
Terapia por Acupuntura , Glaucoma , Atrofia Óptica , Humanos , Células Ganglionares de la Retina , Glaucoma/etiología , Glaucoma/terapia , Atrofia Óptica/etiología , Atrofia Óptica/terapia , Presión IntraocularRESUMEN
Travel entail change in geography and diet, both of which are known as determinant factors in shaping the human gut microbiome. Additionally, altered gut microbiome modulates immunity, bringing about health implications in humans. To explore the effects of the mid-term travel on the gut microbiome, we generated 16S rRNA gene and metagenomic sequencing data from longitudinal samples collected over six months. We monitored dynamic trajectories of the gut microbiome variation of a Chinese volunteer team (VT) in their whole journey to Trinidad and Tobago (TAT). We found gut microbiome resilience that VT's gut microbial compositions gradually transformed to the local TAT's enterotypes during their six-month stay in TAT, and then reverted to their original enterotypes after VT's return to Beijing in one month. Moreover, we identified driven species in this bi-directional plasticity that could play a role in immunity modulation, as exemplified by Bacteroides dorei that attenuated atherosclerotic lesion formation and effectively suppressed proinflammatory immune response. Another driven species P. copri could play a crucial role in rheumatoid arthritis pathogenesis, a chronic autoimmune disease. Carbohydrate-active enzymes are often implicated in immune and host-pathogen interactions, of which glycoside hydrolases were found decreased but glycosyltransferases and carbohydrate esterases increased during the travel; these functions were then restored after VT' returning to Beijing. Furthermore, we discovered these microbial changes and restoration were mediated by VT people's dietary changes. These findings indicate that half-year travel leads to change in enterotype and functional patterns, exerting effects on human health. Microbial intervention by dietary guidance in half-year travel would be conducive to immunity modulation for maintaining health.
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Microbioma Gastrointestinal , Carbohidratos , Heces , Microbioma Gastrointestinal/genética , Humanos , Metagenómica , ARN Ribosómico 16S/genéticaRESUMEN
The retina is sensitive to injury resulting from oxidative stress (OS) due to its high oxygen consumption. Patients with retinitis pigmentosa suffer from excessive OS. Nacetylcysteine (NAC) is used as a mucolytic agent for the clinical treatment of disorders, such as chronic bronchitis and other pulmonary diseases. The aim of the present study was to investigate the role of hexokinase 2 (HKII) in retinal OS injury. Amyloid ß (Aß)140 was used to establish a cellular model of OS. Cell viability was measured with a Cell Counting Kit8 assay, and the apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of cells were analyzed via flow cytometry with corresponding kits. The mRNA and protein levels were detected by reverse transcriptionquantitative PCR and western blot analyses, respectively. It was observed that Aß140 reduced the expression of HKII in the mitochondria of retinal pigment epithelial ARPE cells and impaired mitochondrial antioxidant functions. Additionally, knockdown of HKII promoted apoptosis, and increased ROS levels and the MMP. NAC attenuated the inhibition of mitochondrial functions induced by Aß140. The knockdown of HKII was revealed to decrease the levels of Bcl2, manganese superoxide dismutase (SOD) and copperzincSOD, and increase the levels of cleaved caspase3, Bax and cytochrome c. The present findings suggested that the dissociation of HKII induced by OS induces apoptosis and mitochondrial damage. This study provided improved understanding of the mechanisms underlying the effects of OS on retinal epithelial cells.
Asunto(s)
Hexoquinasa/genética , Estrés Oxidativo , Enfermedades de la Retina/etiología , Enfermedades de la Retina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/farmacología , Apoptosis , Biomarcadores , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Técnicas de Inactivación de Genes , Hexoquinasa/metabolismo , Humanos , Mitocondrias , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Enfermedades de la Retina/patología , Epitelio Pigmentado de la Retina/efectos de los fármacosRESUMEN
The aim of the present study was to compare the changes in the levels of 27 aqueous humor cytokines between diabetic patients with macular edema (ME) and diabetic patients without ME. Undiluted aqueous humor samples were obtained from 68 consecutive type 2 diabetic patients without ME and 56 consecutive type 2 diabetic patients with ME. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. Compared with diabetic patients without ME, diabetic patients with ME had significantly higher concentrations of IL-1ß, IL-6, IL-8, IP-10, MCP-1, and VEGF in the aqueous humor. However, the concentrations of IL-10 and IL-12 were significantly lower in the diabetic patients with ME. The aqueous humor levels of IL-1ß, IL-6, IL-8, MCP-1, IP-10, and VEGF were closely correlated with retinal macular thickness, retinal macular volume and the severity of ME. In addition, the aqueous humor levels of IL-10 and IL-12 decreased with increasing the severity of ME. A variety of cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of diabetic macular edema, and both anti-inflammatory and antiangiogenic agents should be included in the treatment of ME simultaneously.
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Citocinas/biosíntesis , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/genética , Edema Macular/genética , Anciano , Humor Acuoso/metabolismo , Citocinas/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Retinopatía Diabética/etiología , Retinopatía Diabética/patología , Femenino , Humanos , Edema Macular/etiología , Edema Macular/patología , Masculino , Persona de Mediana EdadRESUMEN
This study aims to ascertain whether cytokines in the aqueous humor can predict macular edema (ME) in diabetic patients following uncomplicated phacoemulsification cataract surgery. Undiluted aqueous humor samples were obtained from 136 consecutive type 2 diabetic patients who underwent cataract surgery. The concentrations of 27 cytokines were measured in aqueous humor using the multiplex bead immunoassay. At the final follow-up examination, 116 patients completed 4 weeks of follow-up, and the incidence of macular edema was 29.31% (34 patients) 4 weeks after cataract surgery. Compared to the ME (-) patients, the concentrations of interleukin-1ß (IL-1ß) (P < 0.001), IL-6 (P < 0.001), IL-8 (P < 0.001), interferon-induced protein-10 (IP-10) (P = 0.003), monocyte chemotactic protein-1 (MCP-1) (P < 0.001), and vascular endothelial growth factor (VEGF) (P < 0.001) in the ME (+) patients were significantly higher. In addition, the aqueous levels of IL-1ß (r = 0.288), IL-6 (r = 0.345), IL-8 (r = 0.256), IP-10 (r = 0.377), MCP-1 (r = 0.423), and VEGF (r = 0.279) were positively correlated with the postoperative foveal center point thickness (FCPT). However, the aqueous levels of IL-10 (P = 0.003) and IL-12 (P = 0.017) were significantly lower in patients with ME. These results suggest IL-1ß, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, and VEGF may be potential predictors of postoperative macular thickness in patients with diabetes following uncomplicated phacoemulsification cataract surgery.
Asunto(s)
Humor Acuoso/metabolismo , Extracción de Catarata/efectos adversos , Citocinas/metabolismo , Diabetes Mellitus/etiología , Edema Macular/diagnóstico , Edema Macular/etiología , Facoemulsificación/efectos adversos , Anciano , Diabetes Mellitus/fisiopatología , Retinopatía Diabética/complicaciones , Retinopatía Diabética/fisiopatología , Femenino , Fóvea Central , Humanos , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Agudeza VisualRESUMEN
PURPOSE: Retinal microglia can be activated by retinal neuronal monocyte chemoattractant protein-1 (MCP-1) and play a pivotal role in early retinal degeneration. The current study investigates the pathways via which retinal neuronal MCP-1 stimulates tumor necrosis factor-α (TNF-α) expression in rat microglia. METHODS: Primary rat retinal neurons and microglia were separated and cocultured in a Transwell apparatus. The levels of TNF-α mRNA and soluble TNF-α produced by the microglia in response to advanced glycation end product (AGE)-induced retinal neuronal MCP-1 were measured with real-time PCR and enzyme-linked immunosorbent assay (ELISA). The ability of neuronal MCP-1 to stimulate microglia activation was examined by preexposing the retinal neurons to AGEs and an MCP-1 antibody or by pretreating microglia with AGEs and siRNA specific for CC-chemokine receptor 2 (CCR2) knockdowns. Additionally, we investigated the effects of microglial activation on neuronal MCP-1-induced nuclear factor-κB (NF-κB) activation and phosphorylation of mitogen-activated protein kinases (MAPKs). RESULTS: Stimulation with AGEs significantly increased the expression of TNF-α mRNA and soluble TNF-α in the microglial cells. Retinal neurons that had been pretreated with AGEs and an MCP-1 antibody or microglia that were CCR2 knockdowns displayed greatly reduced TNF-α secretion. Using signaling pathway-specific inhibitors, we showed that blocking the p38, extracellular signal-regulated kinase (ERK), and NF-κB signaling pathways significantly reduced the expression of TNF-α by retinal neuronal MCP-1-stimulated microglia. CONCLUSIONS: This study indicates that TNF-α was released from the activated microglia induced by retinal neuronal MCP-1 via the p38, ERK, and NF-κB pathways, but not c-Jun N-terminal kinase (JNK), which may be an important finding in diabetic retinopathy pathogenesis.
Asunto(s)
Quimiocina CCL2/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Productos Finales de Glicación Avanzada/farmacología , Microglía/metabolismo , FN-kappa B/metabolismo , Neuronas Retinianas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Técnicas de Silenciamiento del Gen , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Microglía/efectos de los fármacos , Microglía/enzimología , Fosforilación/efectos de los fármacos , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores CCR2/metabolismo , Neuronas Retinianas/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
PURPOSE: To ascertain whether cytokines in the aqueous humor can predict macular edema (ME) in non-diabetic patients following uncomplicated phacoemulsification cataract surgery. METHODS: Undiluted aqueous humor samples were obtained from 288 consecutive non-diabetic patients (288 eyes; 132 men and 156 women) who underwent cataract surgery. Macular edema was defined as an increase in the foveal center point thickness (FCPT) more than 30% from the preoperative baseline using optical coherence tomography 4 weeks after cataract surgery. The concentrations of 27 cytokines were measured in aqueous humor samples using the multiplex bead immunoassay. RESULTS: No major intraoperative complications occurred. The incidence of ME was 8.13% (23 patients) 4 weeks after cataract surgery. Compared to the ME (-) patients, the concentrations of interleukin-1ß (IL-1ß; p=0.016), IL-6 (p=0.013), monocyte chemotactic protein-1 (MCP-1; p=0.030), and vascular endothelial growth factor (VEGF; p=0.033) in the ME (+) patients were significantly higher. In addition, the aqueous humor levels of IL-1ß (r=0.376), IL-6 (r=0.418), MCP-1 (r=0.348), and VEGF (r=0.375) positively correlated with the postoperative FCPT. However, the aqueous humor levels of IL-10 (p=0.017) were significantly lower in patients with ME and were negatively correlated with the postoperative FCPT (r=-0.424). CONCLUSIONS: IL-1ß, IL-6, MCP-1, VEGF, and IL-10 may be potential predictors of postoperative macular thickness in non-diabetic patients following uncomplicated phacoemulsification cataract surgery.
Asunto(s)
Humor Acuoso/inmunología , Extracción de Catarata , Citocinas/inmunología , Edema Macular/diagnóstico , Edema Macular/inmunología , Facoemulsificación , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Catarata/inmunología , Catarata/patología , Estudios Transversales , Citocinas/genética , Femenino , Fóvea Central/inmunología , Fóvea Central/patología , Expresión Génica , Humanos , Inmunoensayo , Edema Macular/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To compare the changes in the levels of 27 aqueous humor cytokines between nondiabetic controls and patients with type 2 diabetes and to ascertain the association of these cytokines with diabetic retinopathy (DR). METHODS: Undiluted aqueous humor samples were obtained from 102 nondiabetic patients (102 eyes) and 136 consecutive diabetic patients (136 eyes) who were divided into nine groups according to the Early Treatment of Diabetic Retinopathy Study severity scale. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. RESULTS: Compared with the nondiabetic controls, the diabetic patients had significantly higher concentrations of interleukin-1ß (IL-1ß; p<0.001), IL-6 (p<0.001), IL-8 (p<0.001), monocyte chemoattractant protein-1 (p<0.001), interferon gamma-induced protein-10 (p<0.001), and vascular endothelial growth factor (p<0.001) in the aqueous humor. However, the IL-10 (p=0.002) and IL-12 (p=0.013) concentrations were significantly lower for the diabetic patients. There were no significant differences in the concentrations of other cytokines between the diabetic patients and the controls. The IL-1ß, IL-6, IL-8, monocyte chemoattractant protein-1, and interferon gamma-induced protein-10 levels in the aqueous humor increased as the severity of DR increased. The correlation was significant. However, the vascular endothelial growth factor concentration was not correlated with the severity of DR. In addition, the IL-10 and IL-12 levels in the aqueous humor decreased as the severity of DR increased, and this negative correlation was significant. CONCLUSIONS: Various cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of DR, and chemokines may be more closely related to the development of this disease.
Asunto(s)
Humor Acuoso/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Retinopatía Diabética/complicaciones , Retinopatía Diabética/metabolismo , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/patología , Retinopatía Diabética/patología , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: To explore the relationship between total plasma homocysteine (tHcy) concentration and central retinal vein occlusion (CRVO) in the acute phase in a Chinese population. METHODS: This was a matched case-control study, and participants were recruited between January 2008 and April 2012. The cohort included 68 consecutive patients with CRVO and 68 controls, matched for age and gender, aged 50 years and over. The total plasma homocysteine, vitamin B12 and folate levels and the presence of C677T MTHFR polymorphisms were analyzed in all patients and controls. Fasting venous blood samples were collected within three days after CRVO. RESULTS: There were no significant differences (p = 0.134) in mean plasma tHcy between CRVO patients (10.73 ± 3.21 µmol/l) and controls (9.99 ± 2.57 µmol/l), nor were there any statistically significant differences when subjects were categorized by ischemic and nonischemic CRVO. However, six patients (27.3%) in the ischemic group and three patients (6.5%) in the nonischemic group were found to have hyperhomocysteinemia (p = 0.018). There were no statistically significant differences in serum folate (p = 0.503) or vitamin B12 levels (p = 0.419) between CRVO patients (folate, 5.97 ± 2.06 ng/ml; vitamin B12, 411 ± 122 pg/ml) and controls (folate, 6.18 ± 1.42 ng/ml; vitamin B12, 427 ± 115 pg/ml). The prevalence of the homozygous genotype of the MTHFR C677T mutation was not significantly different in patients than in controls. CONCLUSIONS: We found no association between tHcy in the acute phase after CRVO and CRVO occurrence in a Chinese population, but hyperhomocysteinemia were associated with the development of CRVO.
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Pueblo Asiatico/estadística & datos numéricos , Homocisteína/sangre , Hiperhomocisteinemia/epidemiología , Hiperhomocisteinemia/metabolismo , Oclusión de la Vena Retiniana/epidemiología , Oclusión de la Vena Retiniana/metabolismo , Enfermedad Aguda , Anciano , Pueblo Asiatico/genética , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Femenino , Ácido Fólico/sangre , Genotipo , Humanos , Hiperhomocisteinemia/genética , Hiperlipidemias/epidemiología , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Oclusión de la Vena Retiniana/sangre , Oclusión de la Vena Retiniana/genética , Factores de Riesgo , Vitamina B 12/sangreRESUMEN
PURPOSE: To evaluate the expression of monocyte chemoattractant protein-1 (MCP-1) in the rodent model of diabetic retinopathy (DR) and to study the stimulation of microglial activation by retinal neuronal MCP-1 in vitro. METHODS: Diabetes mellitus was induced by streptozotocin (STZ) injection. The expression of MCP-1 was determined using immunohistochemical methods, Western blotting and RT-PCR analyses. Retinal neurons and microglia were separated and co-cultured in a Transwell apparatus. The levels of soluble MCP-1 that were produced after stimulation of retinal neurons by adding advanced glycation end products (AGEs) to the medium were measured by ELISA. The degree of microglial activation was measured by testing microglial migration and the level of soluble TNF-α in the medium by ELISA. The ability of neuronal MCP-1 to stimulate microglia activation was examined by pre-exposing the retinal neurons to AGEs and an MCP-1 antibody or to AGEs and SiRNA specific to MCP-1. RESULTS: A marked increase in the expression of MCP-1 was detected 4 weeks after STZ injection, and the expression was consistently upregulated at 3 and 5 months in the rodent DR model. Stimulation with AGEs significantly increased the expression of MCP-1 in retinal neurons, which activated microglial cells, including increased microglial migration and upregulated secretion of TNF-α. Retinal neurons that were pre-exposed to AGEs and an MCP-1 antibody or MCP-1 knockdown displayed greatly reduced microglial migration and TNF-α secretion. CONCLUSIONS: Upregulation of MCP-1 began during the early stage of DR and increased with the development of the disease. Retinal neurons are the main source of MCP-1, and they play an important role in retinal microglial activation, which may be an important link in the pathogenesis of DM.
Asunto(s)
Quimiocina CCL2/genética , Diabetes Mellitus Experimental/genética , Retinopatía Diabética/genética , ARN Mensajero/genética , Neuronas Retinianas/metabolismo , Regulación hacia Arriba , Animales , Western Blotting , Supervivencia Celular , Células Cultivadas , Quimiocina CCL2/biosíntesis , Citocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Neuronas Retinianas/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: The Roundabout (Robo) family of proteins is related to the transmembrane receptors and plays a major role in neurogenesis. However, the role of the Robo proteins in proliferative retinopathy has not yet been defined. This study was conducted to determine whether Robo1 is expressed in the retina of patients with proliferative retinal disease and whether it has a pathobiological role in the disease. METHODS: Immunohistochemistry was used to determine the presence and distribution of Robo1 in the pathologic membranes in proliferative retinopathy. Small interfering (si)RNA technology was used to knockdown Robo1 expression and to study its effects on retinal pigment epithelial (RPE) cells in vitro. The impact on PVR development of blocking Robo1 expression was determined by applying specific siRNA in a PVR rabbit model. The prevalences of PVR and retinal detachment were determined by indirect ophthalmoscope on days 1, 3, 7, 14, 21, and 28 after the injection of RPE cells into the vitreous. RESULTS: Immunohistochemistry showed that Robo1 expression was detected in GFAP-labeled glial cells and cytokeratin-labeled RPE cells in proliferative membranes. Robo1 expression was also detected in CD31-labeled vascular endothelial cells. Knockdown of Robo1 expression not only reduced human RPE cell proliferation in vitro but also effectively suppressed the development of PVR in a rabbit model. CONCLUSIONS: Robo1 is present in the extracellular matrix of proliferative membranes and may be derived from dedifferentiated RPE cells. Silencing the expression of Robo1 in RPE cells inhibited cell proliferation and suppressed the development of PVR in an animal model, indicating a potential therapeutic usefulness in treating PVR.
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Modelos Animales de Enfermedad , Proteínas del Tejido Nervioso/fisiología , Receptores Inmunológicos/fisiología , Epitelio Pigmentado de la Retina/metabolismo , Vitreorretinopatía Proliferativa/metabolismo , Adolescente , Anciano , Animales , Línea Celular , Movimiento Celular , Proliferación Celular , Niño , Retinopatía Diabética/metabolismo , Endotelio Vascular/metabolismo , Ensayo de Inmunoadsorción Enzimática , Membrana Epirretinal/metabolismo , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Indirecta , Silenciador del Gen/fisiología , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Queratinas/metabolismo , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , ARN Interferente Pequeño/genética , Conejos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vitreorretinopatía Proliferativa/prevención & control , Adulto Joven , Proteínas RoundaboutRESUMEN
BACKGROUND/AIMS: Chemokines play a critical role in inflammation and neurodegenerative disease in the central nervous system. In this study, endotoxin-induced uveitis (EIU) was induced to test the expression of fractalkine, a special neuronal chemokine, and its receptor CX3CR1 in acute inflammation of the retina. METHODS: EIU was induced by footpad injections of lipopolysaccharide (LPS). Eight rats were sacrificed at each time point (0, 8, 16, 24, 48, and 72 h) after LPS injection. Sections were made for histopathological tests. Immunohistochemistry was performed using antibodies specific to fractalkine and CX3CR1. Retinas were collected, and total protein and mRNA from both the induced and control rats were extracted. mRNA and protein expression of fractalkine and CX3CR1 in the retina were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blots, respectively. RESULTS: The EIU model was successfully induced. In control rats, both fractalkine and its receptor CX3CR1 were detected in the retina. LPS injection induced a transient upregulation of both proteins at 24 h as determined by the increased number of positively stained cells as well as increased levels of mRNA and protein (p < 0.05). CONCLUSION: A transitory increased expression of fractalkine and its receptor CX3CR1 occurred at the crest time of EIU, and this change in expression may play a role in the turnover of LPS-induced acute retina inflammation.
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Quimiocina CX3CL1/biosíntesis , Lipopolisacáridos/efectos adversos , Receptores de Quimiocina/biosíntesis , Uveítis/metabolismo , Animales , Western Blotting , Receptor 1 de Quimiocinas CX3C , Quimiocina CX3CL1/química , Quimiocina CX3CL1/genética , Femenino , Regulación de la Expresión Génica , Inmunohistoquímica , Iris/metabolismo , Iris/patología , Lipopolisacáridos/administración & dosificación , ARN Mensajero/biosíntesis , Ratas , Ratas Endogámicas Lew , Receptores de Quimiocina/química , Receptores de Quimiocina/genética , Retina/metabolismo , Retina/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Uveítis/inducido químicamenteRESUMEN
BACKGROUND: T lymphocytes have been implicated in the development of endotoxin-induced uveitis (EIU). T-bet is a Th1 cell-specific transcription factor that is involved in differentiation and effector functions. The aim of this study was to investigate kinetics of T-bet expression at the mRNA and protein levels during EIU using real-time PCR and whole-mount immunohistochemistry. METHODS: A single footpad injection of 200 mug of lipopolysaccharide (LPS) was administered to male Wistar rats in order to induce EIU. Clinical changes were followed by slit-lamp examination. The expression of T-bet mRNA in the spleen was evaluated 0, 8, 16, 24, 48, and 96 h after LPS injection using real-time PCR. Immunohistochemistry was performed on the iris whole-mounts as well as on frozen sections of the spleen to evaluate T-bet protein expression. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed on the iris whole-mounts to assay apoptotic cells. RESULTS: Uveitis was observed in all rats that received LPS. T-bet(+) cells and TUNEL(+) cells in the iris whole-mounts showed a similar pattern in cell number and distribution and both types of cells were observed at 8 h, significantly increased 24 h, and decreased 48 h after LPS injection. T-bet expression at both the mRNA and protein levels in spleen also paralleled ocular inflammation. It was weakly detectable after 0 h, increased after 8 h (index 1.3, T-bet(+) cells OD 17.43+/-2.15), reached its peak after 24 h (index 4.00, OD 53.52+/-4.00), and decreased 48 h following LPS injection (index 1.38, OD 25.75+/-2.45). CONCLUSIONS: The results show that T-bet expression in both the iris and the spleen, and in apoptotic cells in the iris parallel the severity of intraocular inflammation after systemic LPS administration. These results suggest that T-bet may play a significant role in the dynamics of EIU.
Asunto(s)
Regulación de la Expresión Génica/fisiología , Iris/metabolismo , Bazo/metabolismo , Proteínas de Dominio T Box/genética , Uveítis/genética , Animales , Apoptosis , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Iris/patología , Lipopolisacáridos , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Salmonella typhimurium , Bazo/patología , Proteínas de Dominio T Box/metabolismo , Uveítis/inducido químicamente , Uveítis/patologíaRESUMEN
OBJECTIVE: To quantify aqueous flare and cells in the eyes of patients with inflammation of anterior uvea by FC-2000 laser flare cell meter (LFCM), and to compare these results with those obtained with slit lamp microscopy. METHODS: Aqueous flare and cells of 194 eyes of 110 patients with inflammation of anterior uvea and 52 eyes of 52 healthy subjects were graded into 0, 1+, 2+, 3+ and 4 + scale based on a previously described system using slit lamp microscopy. LFCM was also used for evaluation of aqueous flare and cells. RESULTS: All eyes in normal individuals were graded as "0" scale of both flare and cells by silt lamp microscopy. Flare of grade 0, 1+ and 2+ were noted in 74, 98 and 18 eyes, and cell of grade 0, 1+, 2+, 3+ and 4+ were noted in 124, 26, 19, 14 and 11 eyes in uveitis patients, respectively. LFCM examination revealed that the mean flare values in uveitis eyes with flare of grade 0, 1+ and 2+ were 7.9, 29.5 and 189.0 photon count/ms, respectively. In patients with flare of grade 3+ and 4+, LFCM readings were unreliable because of increased background noise. There was significant correlation between slit lamp examination and the laser flare measurement for flare of grade 0, 1+ and 2+ (r = 0.75, P < 0.001). The mean flare values were significantly higher in patients with flare of grade 0, 1+ and 2+ than that in normal controls (5.3 pc/ms) (t = 5.872, P < 0.05). The mean cell numbers in the eyes with cell of grade 0, 1+, 2+, 3+ and 4+ were 1.5, 12.1, 33.9, 84.9 and 193.1 count/0.5 mm(3), respectively. The results of slit lamp examination showed significant correlation with laser cell counts measurement (r = 0.72, P < 0.001). The mean cell numbers were significantly higher in uveitis patients than that in normal controls (0.9 count/0.5 mm(3)) (t = 7.351, P < 0.05). CONCLUSIONS: Our results indicate that LFCM is able to evaluate precisely the mild and moderate breakdown of blood aqueous barrier and inflammation of the anterior uvea tract, therefore it provides an important parameter for the treatment of anterior uveitis.