Purpose : We studied the pathogenesis of glucocorticoid-induced glucoma (GIG) through characterization of glucocorticoid receptor (GR) on lymphocytes in Chinese patients with GIG.Methods:By radioligand receptor bindin...Purpose : We studied the pathogenesis of glucocorticoid-induced glucoma (GIG) through characterization of glucocorticoid receptor (GR) on lymphocytes in Chinese patients with GIG.Methods:By radioligand receptor binding followed by Scatchard analysis, the specific binding sites were characterized and quantitated for glucocorticoid receptors on peripheral blood lymphocytes obtained from patients with GIG and the control group.Results:The binding sites we detected were as follows; 12.7 ± 1.47 × 103 receptors per cell with a KD of 3.02 ± 0.62nmol/L in patients with GIG, 7.26 ± 0.45 × 103 receptors per cell with a KD of 3.03 ± 0.56nmol/L in the control group. The statistical difference of receptors per cell is significant between two groups (p < 0.05), patients with GIG having more GR binding sites, while the difference of Kd is not significant ( p > 0.05 ) . Conclusion: The preliminary findings suggest that patients with GIG are more sensitive to glucocorticoid and the increase of binding sites of展开更多
AIM: To avoid the side effects of ocular hypertension of glucocorticoid(GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all prima...AIM: To avoid the side effects of ocular hypertension of glucocorticoid(GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all primary open angle glaucoma(POAG) patients show this phenotype.Glucocorticoid receptor(GR) regulates C responsiveness in trabecular meshwork(TM) cells. In this study, single nucleotide polymorphism(SNP) genotyping was used to determine whether there are differences in the Bcl I(rs41423247) and N363S(rs6195) polymorphisms of the GR gene in healthy and POAG patients, and glucocorticoid-induced ocular hypertension(GIOH)populations.METHODS: Three hundred and twenty-seven unrelated Chinese adults, including 111 normal controls, 117 GIOH subjects and 99 POAG patients, were recruited. DNA samples were prepared and the Bcl I and N363 S polymorphisms were screened using real-time polymerase chain reaction(RT-PCR)-restriction fragment length polymorphism(RFLP) analysis. Frequencies of the Bcl I and N363 S polymorphisms were determined and compared using Fisher’s exact test and the Chi-squared test.RESULTS: Only the Bcl I polymorphism was identified in the Chinese Han population. The frequency of the G allele was 21.6 % in normal controls, 18.3% in GIOH patients, and 13.64% in the POAG patients. There was no significant difference in polymorphism or allele frequency in the 3 groups. Furthermore, no N363 S polymorphism was found in the study subjects.CONCLUSION: The Bcl I polymorphisms in GR gene had no association with GIOH and POAG patients, and N363 S polymorphism might not exist in the Chinese Han population. Therefore, the Bcl I polymorphism might not be responsible for the development of GC-induced ocular hypertension or POAG.展开更多
Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal indivi...Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal individuals and patients with GIG were cultured in vitro. By using polymerase chain reaction (PCR),gene fragments on GR DNA binding sites of trabecular cells were amplified. The product was detected by gel electrophoresis.Results: The trabecular cells were cultured successfully in normal individuals and patients with GIG in vitro. A single PCR product was obtained in both two groups with the same size of 545 base pairs.Conclusion: There is not any difference in gene on the GR DNA binding sites between normal individuals and patients with GIG. The results suggest the difference in mRNA or other functional genes. Eye Science 1999 ; 15 ; 46 - 50.展开更多
糖皮质激素(glucocorticoids,GCs)作用于小梁网组织,诱导发生组织形态学的改变与功能失衡。研究证实糖皮质激素性青光眼与原发性开角型青光眼(primary open angle glaucoma,POAG)具有相似的小梁网形态与功能变化,然而POAG的发病机制仍...糖皮质激素(glucocorticoids,GCs)作用于小梁网组织,诱导发生组织形态学的改变与功能失衡。研究证实糖皮质激素性青光眼与原发性开角型青光眼(primary open angle glaucoma,POAG)具有相似的小梁网形态与功能变化,然而POAG的发病机制仍不清楚。阐明GCs如何诱导小梁网形态学的改变,如何影响房水流出阻力,有利于探索POAG的发病机制。文章主要就GCs对小梁网的影响作一综述。展开更多
目的验证受体结合试验检测的糖皮质激素受体(GR)的特异性,从受体水平探索皮质类固醇性青光眼治疗的新途径。方法用Ru38486,通过受体的竞争抑制试验,检测皮质类固醇性青光眼患者、正常人外周血淋巴细胞GR的半数抑制量(IC50)和平衡抑制常...目的验证受体结合试验检测的糖皮质激素受体(GR)的特异性,从受体水平探索皮质类固醇性青光眼治疗的新途径。方法用Ru38486,通过受体的竞争抑制试验,检测皮质类固醇性青光眼患者、正常人外周血淋巴细胞GR的半数抑制量(IC50)和平衡抑制常数(KI),并将检测结果作统计分析。结果皮质类固醇性青光眼患者、正常人外周血淋巴细胞GR的IC50分别为(224.30±18.79)nmol/L和(195.99±16.08)nmol/L,KI分别为(44.56±5.10)nmol/L和(37. 88±2.79)nmol/L,差异均有显著性( P <0.05);两组样本的竞争抑制曲线为“S”形。结论受体结合试验检测的GR为糖皮质激素(GC)特异性受体,从受体的竞争性角度证明皮质类固醇性青光眼患者外周血淋巴细胞GR的结合位点高于正常人,GR特性检测可能成为皮质类固醇性青光眼诊断和鉴别诊断的客观标准,GR拮抗剂可望发展成为治疗皮质类固醇性青光眼和其他类型青光眼的新途径。展开更多
基金This paper was supported by Natural Science Foundation of Guangdong Province (940547)
文摘Purpose : We studied the pathogenesis of glucocorticoid-induced glucoma (GIG) through characterization of glucocorticoid receptor (GR) on lymphocytes in Chinese patients with GIG.Methods:By radioligand receptor binding followed by Scatchard analysis, the specific binding sites were characterized and quantitated for glucocorticoid receptors on peripheral blood lymphocytes obtained from patients with GIG and the control group.Results:The binding sites we detected were as follows; 12.7 ± 1.47 × 103 receptors per cell with a KD of 3.02 ± 0.62nmol/L in patients with GIG, 7.26 ± 0.45 × 103 receptors per cell with a KD of 3.03 ± 0.56nmol/L in the control group. The statistical difference of receptors per cell is significant between two groups (p < 0.05), patients with GIG having more GR binding sites, while the difference of Kd is not significant ( p > 0.05 ) . Conclusion: The preliminary findings suggest that patients with GIG are more sensitive to glucocorticoid and the increase of binding sites of
文摘AIM: To avoid the side effects of ocular hypertension of glucocorticoid(GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all primary open angle glaucoma(POAG) patients show this phenotype.Glucocorticoid receptor(GR) regulates C responsiveness in trabecular meshwork(TM) cells. In this study, single nucleotide polymorphism(SNP) genotyping was used to determine whether there are differences in the Bcl I(rs41423247) and N363S(rs6195) polymorphisms of the GR gene in healthy and POAG patients, and glucocorticoid-induced ocular hypertension(GIOH)populations.METHODS: Three hundred and twenty-seven unrelated Chinese adults, including 111 normal controls, 117 GIOH subjects and 99 POAG patients, were recruited. DNA samples were prepared and the Bcl I and N363 S polymorphisms were screened using real-time polymerase chain reaction(RT-PCR)-restriction fragment length polymorphism(RFLP) analysis. Frequencies of the Bcl I and N363 S polymorphisms were determined and compared using Fisher’s exact test and the Chi-squared test.RESULTS: Only the Bcl I polymorphism was identified in the Chinese Han population. The frequency of the G allele was 21.6 % in normal controls, 18.3% in GIOH patients, and 13.64% in the POAG patients. There was no significant difference in polymorphism or allele frequency in the 3 groups. Furthermore, no N363 S polymorphism was found in the study subjects.CONCLUSION: The Bcl I polymorphisms in GR gene had no association with GIOH and POAG patients, and N363 S polymorphism might not exist in the Chinese Han population. Therefore, the Bcl I polymorphism might not be responsible for the development of GC-induced ocular hypertension or POAG.
基金by grants from Nature Science Fundation of China Guangdong province (No.39800163 and No.980112)
文摘Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal individuals and patients with GIG were cultured in vitro. By using polymerase chain reaction (PCR),gene fragments on GR DNA binding sites of trabecular cells were amplified. The product was detected by gel electrophoresis.Results: The trabecular cells were cultured successfully in normal individuals and patients with GIG in vitro. A single PCR product was obtained in both two groups with the same size of 545 base pairs.Conclusion: There is not any difference in gene on the GR DNA binding sites between normal individuals and patients with GIG. The results suggest the difference in mRNA or other functional genes. Eye Science 1999 ; 15 ; 46 - 50.
文摘糖皮质激素(glucocorticoids,GCs)作用于小梁网组织,诱导发生组织形态学的改变与功能失衡。研究证实糖皮质激素性青光眼与原发性开角型青光眼(primary open angle glaucoma,POAG)具有相似的小梁网形态与功能变化,然而POAG的发病机制仍不清楚。阐明GCs如何诱导小梁网形态学的改变,如何影响房水流出阻力,有利于探索POAG的发病机制。文章主要就GCs对小梁网的影响作一综述。
文摘目的验证受体结合试验检测的糖皮质激素受体(GR)的特异性,从受体水平探索皮质类固醇性青光眼治疗的新途径。方法用Ru38486,通过受体的竞争抑制试验,检测皮质类固醇性青光眼患者、正常人外周血淋巴细胞GR的半数抑制量(IC50)和平衡抑制常数(KI),并将检测结果作统计分析。结果皮质类固醇性青光眼患者、正常人外周血淋巴细胞GR的IC50分别为(224.30±18.79)nmol/L和(195.99±16.08)nmol/L,KI分别为(44.56±5.10)nmol/L和(37. 88±2.79)nmol/L,差异均有显著性( P <0.05);两组样本的竞争抑制曲线为“S”形。结论受体结合试验检测的GR为糖皮质激素(GC)特异性受体,从受体的竞争性角度证明皮质类固醇性青光眼患者外周血淋巴细胞GR的结合位点高于正常人,GR特性检测可能成为皮质类固醇性青光眼诊断和鉴别诊断的客观标准,GR拮抗剂可望发展成为治疗皮质类固醇性青光眼和其他类型青光眼的新途径。
