AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithe...AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithelial(hRPE)cells.METHODS:Cells were cultured with either normal(5 mmol/L)or high D-glucose(25 mmol/L)concentrations for 8d to establish control and high-glucose groups,respectively.To induce metabolic memory,cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d.In addition,exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control,miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d.Quantitative reverse transcription-polymerase chain reaction(RT-qPCR)was used to detect miR-204 mRNA levels.SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot.Flow cytometry was used to investigate apoptosis rate.RESULTS:It was found that high glucose promoted miR-204 and VEGF expression,and inhibited SIRT1 activity,even after the return to normal glucose culture conditions.Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression.However,downregulation of miR-204 produced the opposite effects.CONCLUSION:The study identifies that miR-204 is the upstream target of SIRT1and VEGF,and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.展开更多
Dear Editor,We report a case of traumatic carotid cavernous fistula(CCF)that initially presented in the Ophthalmology Department because of the ocular manifestations.CFF is a clinical syndrome characterized by ocular ...Dear Editor,We report a case of traumatic carotid cavernous fistula(CCF)that initially presented in the Ophthalmology Department because of the ocular manifestations.CFF is a clinical syndrome characterized by ocular abnormalities,which is caused by abnormal communication between the cavernous sinus and the cavernous segment or other meningeal branches of the internal carotid artery(ICA)due to traumatic or spontaneous factors.展开更多
Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye diseasewith an unknown etiology. Understanding its genomic and epigenomic landscape could aid indeveloping etiology-based therapies. In this...Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye diseasewith an unknown etiology. Understanding its genomic and epigenomic landscape could aid indeveloping etiology-based therapies. In this study, we recruited 99 ICE patients and performedwhole-genome sequencing (WGS) on 51 and genome-wide DNA methylation profiling on 48 ofthem. We conducted mutational burden testing on genes and noncoding regulatory regions,comparing the ICE cohort with control groups (9197 East Asians from the gnomAD databaseand 350 normal Chinese from our in-house cohort). Copy number variation (CNV) analysisand differential methylation of regions were also explored. We identified RP1L1 (27/51,53%) with a significantly higher coding-altering mutational burden in the ICE cohort (p <8.3×10^(7)), with mutations predominantly at chr8:10467637 (hg19). Additionally, 41 regionswith significant CNVs were identified, including two regions at chr19:15783859-15791329(hg19) and chr3:75786061-75790887 (hg19), showing copy number loss in 39 and 19 patients,respectively. We also identified 2,717 differentially methylated regions (DMRs), with hypomethylation prevalent in ICE syndrome (91.9% of DMRs). Among these, 45 recurrent hypomethylated regions (HMRs) in more than 10% of ICE patients showed differential methylationcompared to normal controls. This study presents the first comprehensive genomic and epigenomic characterization of ICE syndrome, offering insights into its underlying etiology.展开更多
基金Supported by the Training Project for Young and Middleaged Core Talents in Health System of Fujian Province(No.2016-ZQN-62)Natural Science Foundation of Fujian Province(No.2020J01652).
文摘AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithelial(hRPE)cells.METHODS:Cells were cultured with either normal(5 mmol/L)or high D-glucose(25 mmol/L)concentrations for 8d to establish control and high-glucose groups,respectively.To induce metabolic memory,cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d.In addition,exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control,miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d.Quantitative reverse transcription-polymerase chain reaction(RT-qPCR)was used to detect miR-204 mRNA levels.SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot.Flow cytometry was used to investigate apoptosis rate.RESULTS:It was found that high glucose promoted miR-204 and VEGF expression,and inhibited SIRT1 activity,even after the return to normal glucose culture conditions.Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression.However,downregulation of miR-204 produced the opposite effects.CONCLUSION:The study identifies that miR-204 is the upstream target of SIRT1and VEGF,and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.
文摘Dear Editor,We report a case of traumatic carotid cavernous fistula(CCF)that initially presented in the Ophthalmology Department because of the ocular manifestations.CFF is a clinical syndrome characterized by ocular abnormalities,which is caused by abnormal communication between the cavernous sinus and the cavernous segment or other meningeal branches of the internal carotid artery(ICA)due to traumatic or spontaneous factors.
基金supported by the National Key Research and Development Program of China(No.2022YFC2502800)the National Natural Science Foundation of China(No.82070955,32000537).
文摘Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye diseasewith an unknown etiology. Understanding its genomic and epigenomic landscape could aid indeveloping etiology-based therapies. In this study, we recruited 99 ICE patients and performedwhole-genome sequencing (WGS) on 51 and genome-wide DNA methylation profiling on 48 ofthem. We conducted mutational burden testing on genes and noncoding regulatory regions,comparing the ICE cohort with control groups (9197 East Asians from the gnomAD databaseand 350 normal Chinese from our in-house cohort). Copy number variation (CNV) analysisand differential methylation of regions were also explored. We identified RP1L1 (27/51,53%) with a significantly higher coding-altering mutational burden in the ICE cohort (p <8.3×10^(7)), with mutations predominantly at chr8:10467637 (hg19). Additionally, 41 regionswith significant CNVs were identified, including two regions at chr19:15783859-15791329(hg19) and chr3:75786061-75790887 (hg19), showing copy number loss in 39 and 19 patients,respectively. We also identified 2,717 differentially methylated regions (DMRs), with hypomethylation prevalent in ICE syndrome (91.9% of DMRs). Among these, 45 recurrent hypomethylated regions (HMRs) in more than 10% of ICE patients showed differential methylationcompared to normal controls. This study presents the first comprehensive genomic and epigenomic characterization of ICE syndrome, offering insights into its underlying etiology.
