目的利用两样本孟德尔随机化(MR)分析阿尔茨海默病(AD)与年龄相关性黄斑变性(AMD)之间存在的潜在因果关联。方法使用IEU Open GWAS数据库AD和干性AMD、湿性AMD全基因组关联研究的汇总统计数据,使用单核苷酸多态性(SNP)作为因果推断的工...目的利用两样本孟德尔随机化(MR)分析阿尔茨海默病(AD)与年龄相关性黄斑变性(AMD)之间存在的潜在因果关联。方法使用IEU Open GWAS数据库AD和干性AMD、湿性AMD全基因组关联研究的汇总统计数据,使用单核苷酸多态性(SNP)作为因果推断的工具变量,进行两样本MR分析。采用逆方差加权法(IVW)评估AD与湿性AMD、干性AMD的是否存在因果关联,同时采用MR-Egger回归法、加权中位数法(WME)、异质性检验及敏感性分析对结果进行补充分析。结果(1)筛选结果:暴露因素中,AD、湿性AMD、干性AMD均筛选出13个SNP。(2)AD与湿性AMD:AD与湿性AMD发生的强相关因素,有统计学意义[OR=0.883,95%CI(0.784,0.885),F=34.848,P=0.000],MR-Egger回归法显示不存在水平多效性(P>0.05),且AD与湿性AMD散点图斜率为负,表明二者存在因果关系。(3)AD与干性AMD:AD与干性AMD发生的强相关因素,有统计学意义[OR=0.875,95%CI(0.828,0.925),F=22.563,P=0.000],MR-Egger回归法显示不存在水平多效性(P>0.05),且AD与干性AMD散点图斜率为负,表明二者存在因果关系。结论AD与AMD存在潜在联系。由于AMD具有高致盲性,认识和控制AMD危险因素,阐明这两种疾病的共同致病途径将有助于其预防、治疗的研究。展开更多
Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal deg...Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.展开更多
Dear Editor,Torpedo maculopathy(TM),first described by Roseman and Gass in 1992[1],is a rare congenital unilateral retinal pigment epithelium(RPE)abnormality.The term“torpedo maculopathy”was coined by Daily[2]in 199...Dear Editor,Torpedo maculopathy(TM),first described by Roseman and Gass in 1992[1],is a rare congenital unilateral retinal pigment epithelium(RPE)abnormality.The term“torpedo maculopathy”was coined by Daily[2]in 1993.TM typically spares the foveal center,is asymptomatic,and is often detected incidentally during routine ophthalmic examinations.Through literature search,we did not identify racial or regional differences in TM.It predominantly affects children,with an estimated prevalence of 2 per 100000 in individuals under 16 ages[3].While previous reports have focused on pediatric and adult populations,this study presents four cases of TM in preterm infants.展开更多
文摘目的利用两样本孟德尔随机化(MR)分析阿尔茨海默病(AD)与年龄相关性黄斑变性(AMD)之间存在的潜在因果关联。方法使用IEU Open GWAS数据库AD和干性AMD、湿性AMD全基因组关联研究的汇总统计数据,使用单核苷酸多态性(SNP)作为因果推断的工具变量,进行两样本MR分析。采用逆方差加权法(IVW)评估AD与湿性AMD、干性AMD的是否存在因果关联,同时采用MR-Egger回归法、加权中位数法(WME)、异质性检验及敏感性分析对结果进行补充分析。结果(1)筛选结果:暴露因素中,AD、湿性AMD、干性AMD均筛选出13个SNP。(2)AD与湿性AMD:AD与湿性AMD发生的强相关因素,有统计学意义[OR=0.883,95%CI(0.784,0.885),F=34.848,P=0.000],MR-Egger回归法显示不存在水平多效性(P>0.05),且AD与湿性AMD散点图斜率为负,表明二者存在因果关系。(3)AD与干性AMD:AD与干性AMD发生的强相关因素,有统计学意义[OR=0.875,95%CI(0.828,0.925),F=22.563,P=0.000],MR-Egger回归法显示不存在水平多效性(P>0.05),且AD与干性AMD散点图斜率为负,表明二者存在因果关系。结论AD与AMD存在潜在联系。由于AMD具有高致盲性,认识和控制AMD危险因素,阐明这两种疾病的共同致病途径将有助于其预防、治疗的研究。
基金supported by the National Natural Science Foundation of China,Nos.82171076(to XS)and U22A20311(to XS),82101168(to TL)Shanghai Science and technology Innovation Action Plan,No.23Y11901300(to JS)+1 种基金Science and Technology Commission of Shanghai Municipality,No.21ZR1451500(to TL)Shanghai Pujiang Program,No.22PJ1412200(to BY)。
文摘Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.
基金Supported by the National Natural Science Foundation of China(No.82070991).
文摘Dear Editor,Torpedo maculopathy(TM),first described by Roseman and Gass in 1992[1],is a rare congenital unilateral retinal pigment epithelium(RPE)abnormality.The term“torpedo maculopathy”was coined by Daily[2]in 1993.TM typically spares the foveal center,is asymptomatic,and is often detected incidentally during routine ophthalmic examinations.Through literature search,we did not identify racial or regional differences in TM.It predominantly affects children,with an estimated prevalence of 2 per 100000 in individuals under 16 ages[3].While previous reports have focused on pediatric and adult populations,this study presents four cases of TM in preterm infants.
