AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHO...AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHODS:Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed.They were randomized to receive one of the following treatments:0.9%normal saline,one of 1-,5-,and 10μmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1,2,3,5,and 7,and TA immediately after surgery.As a control group,unoperated left eyes(n=6)were used.On the 28 th day,six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes,fibrosis and adhesion.Transforming growth factor beta,matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.RESULTS:Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline(sham)group.Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10μmol nintedanib group.Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis.Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion.The expressions of transforming growth factor beta,alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.CONCLUSION:Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery.Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to steroids.Further investigation is needed to prove antiadhesive effect of nintedanib.展开更多
目的通过候选基因法对2个中国籍先天性眼外肌纤维化(congenital fibrosis of the extraocular muscles,CFEOM)家系进行致病基因定位及疾病分型。方法对2个CFEOM家系所有成员均采集病史、体格检查、抽取外周静脉血5~8 mL并提取基因组DNA...目的通过候选基因法对2个中国籍先天性眼外肌纤维化(congenital fibrosis of the extraocular muscles,CFEOM)家系进行致病基因定位及疾病分型。方法对2个CFEOM家系所有成员均采集病史、体格检查、抽取外周静脉血5~8 mL并提取基因组DNA。选择KIF21A第2、8、20、21外显子;PHOX2A/ARIX第1、2、3外显子;TUBB2B第1、2、3、4外显子;TUBB3第1、2、3、4外显子区域进行PCR引物合成并将扩增样品进行纯化测序,结果应用Chromas 2.3及DNAman 7.0软件进行序列比对分析。结果家系1五代中9人患病,均具有典型CFEOM外观特征。致病基因位于KIF21A基因外显子21,2860C>T。家系2四代中4人患病,除1人临床表型不典型外,其他3人都具有典型的CFEOM外观特征。致病基因位于TUBB3基因外显子4,1249G>A。结论运用候选基因法可快捷、有效地确定遗传性疾病家系的致病基因。家系1属于CFEOM 1A型,为常染色体完全外显的显性遗传;家系2属于CFEOM 3A型,为常染色体不完全外显的显性遗传。展开更多
目的分析一个中国人先天性眼外肌纤维化(congenital fibrosis of extraocularmuscles,CFEOM)家系的临床表型,并通过基因连锁分析的方法对该家系的致病基因进行定位研究。方法收集一个CFEOM家系,对家系所有成员进行详细的临床检查。确定...目的分析一个中国人先天性眼外肌纤维化(congenital fibrosis of extraocularmuscles,CFEOM)家系的临床表型,并通过基因连锁分析的方法对该家系的致病基因进行定位研究。方法收集一个CFEOM家系,对家系所有成员进行详细的临床检查。确定其临床表型及遗传方式后,在位于11号染色体的已知CFEOM基因附近选取微卫星标记物进行连锁分析。运用MILINK软件计算最大优势对数LOD值。结果该家系的遗传方式为常染色体隐性遗传,家系中的5例患者均表现为典型的眼外肌纤维化特征。与该家系连锁的染色体微卫星标记物为D11S4151和D11S1320,其最大的LOD值为1.21。结论此家系为常染色体隐性遗传型CFEOM2型,其致病基因位于11号染色体的D11S4151和D11S1320之间,位于该区间内的已知基因PHOX2A/ARIX的突变可能是导致该家系致病的分子基础。展开更多
基金Supported by Kocaeli University Scientific Research Projects Unit Fund(No.2019/029)。
文摘AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHODS:Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed.They were randomized to receive one of the following treatments:0.9%normal saline,one of 1-,5-,and 10μmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1,2,3,5,and 7,and TA immediately after surgery.As a control group,unoperated left eyes(n=6)were used.On the 28 th day,six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes,fibrosis and adhesion.Transforming growth factor beta,matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.RESULTS:Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline(sham)group.Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10μmol nintedanib group.Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis.Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion.The expressions of transforming growth factor beta,alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.CONCLUSION:Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery.Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to steroids.Further investigation is needed to prove antiadhesive effect of nintedanib.
文摘目的分析一个中国人先天性眼外肌纤维化(congenital fibrosis of extraocularmuscles,CFEOM)家系的临床表型,并通过基因连锁分析的方法对该家系的致病基因进行定位研究。方法收集一个CFEOM家系,对家系所有成员进行详细的临床检查。确定其临床表型及遗传方式后,在位于11号染色体的已知CFEOM基因附近选取微卫星标记物进行连锁分析。运用MILINK软件计算最大优势对数LOD值。结果该家系的遗传方式为常染色体隐性遗传,家系中的5例患者均表现为典型的眼外肌纤维化特征。与该家系连锁的染色体微卫星标记物为D11S4151和D11S1320,其最大的LOD值为1.21。结论此家系为常染色体隐性遗传型CFEOM2型,其致病基因位于11号染色体的D11S4151和D11S1320之间,位于该区间内的已知基因PHOX2A/ARIX的突变可能是导致该家系致病的分子基础。
