Dear Editor,We report a rare case of lens coloboma and several notches with bilateral ectopia lentis in Marfan syndrome.This case was approved by the Ethics Committee of Aier Excellence Eye Hospital(2023KJB0004).Writt...Dear Editor,We report a rare case of lens coloboma and several notches with bilateral ectopia lentis in Marfan syndrome.This case was approved by the Ethics Committee of Aier Excellence Eye Hospital(2023KJB0004).Written informed consent was obtained from the patient.Lens coloboma and Marfan syndrome are of low incidence and seldom observed in the clinic.展开更多
Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role ...Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We uncovered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.展开更多
基金Supported by Hunan Province Enterprise Joint Fund Project(No.2023JJ70040)Young and Middle-Aged Science and Technology Innovation Incubation Project of Aier Eye Group(No.AC2214D01)+1 种基金Free Exploration Program of the Scientific Research Foundation of Aier Eye Group in 2021(No.AF2102D6)Clinical Research Institute Research Fund Project of Aier Eye Group(No.AR2102D1).
文摘Dear Editor,We report a rare case of lens coloboma and several notches with bilateral ectopia lentis in Marfan syndrome.This case was approved by the Ethics Committee of Aier Excellence Eye Hospital(2023KJB0004).Written informed consent was obtained from the patient.Lens coloboma and Marfan syndrome are of low incidence and seldom observed in the clinic.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82000429 and 81470574)Young Elite Scientists Sponsorship Program by CAST,China(Program No.:YESS20230395/2023QNRC001)+4 种基金Beijing Nova Program,China(Program No.:20230484308)Youth Elite Program of Beijing Friendship Hospital,China(Program No.:YYQCJH2022-9)Young Elite Scientists Sponsorship Program by BAST,China(Program No.:BYESS2024045)Capital's Funds for Health Improvement and Research,China(Grant No.:CFH2022-4-20217)Chinese Institutes for Medical Research,Beijing(CIMR)Organized Research Project,China(Project No.:CX23YQ07)。
文摘Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We uncovered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.
