Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the h...Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the host microenvironment,which in turn affects the functionality of transplanted human neural stem/progenitor cells and potentially limits their benefits for neurorepair.However,the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood.Here,we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment.Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3.ID3-depleted human neural stem/progenitor cells,generated by CRISPR/Cas9-mediated genome editing,reduced astrocyte formation in response to astrogenic stimuli.Instead,ID3-depleted human neural stem/progenitor cells had a bipolar,immature glial progenitor cell phenotype.These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth.We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells,potentially enhancing their capacity to promote central nervous system repair.展开更多
AIM:To evaluate functional outcome of sutureless scleral tunnel intraocular lens(SSTIOL)in children with crystalline lens subluxation of more than 7 clock hours.METHODS:A prospective interventional study was conducted...AIM:To evaluate functional outcome of sutureless scleral tunnel intraocular lens(SSTIOL)in children with crystalline lens subluxation of more than 7 clock hours.METHODS:A prospective interventional study was conducted consisting of 45 eyes of 44 children in age group 6-18 y having>7 clock hours of lens subluxation who underwent lensectomy-vitrectomy followed by SSTIOL implantation.Primary outcome was improvement in best corrected visual acuity(BCVA)and secondary outcomes were assessment of intraocular lens(IOL)tilt using ultrasound biomicroscopy(UBM),mean change in astigmatism at last follow-up of 1 y and associated complications.RESULTS:The mean preoperative and postoperative BCVA was 1.05±0.28 and 0.64±0.45(log MAR)respectively(P=0.001)at last follow-up.The mean astigmatism preoperatively and postoperatively was-4.17±2.69 D and-1.86±1.25 D respectively(P=0.011).Significant IOL tilt(>5 degrees)was present in 5 cases.The mean percentage endothelial loss was 3.65%±1.92%.The most serious complication encountered was retinal detachment seen in 2 cases.CONCLUSION:SSTIOL implantation provides efficient visual rehabilitation in children provided there is stringent case selection.We recommend caution in children having white-to-white distance>12 mm and presence of peripheral retinal degenerations.展开更多
AIM:To compare outcomes of conventional and Hangback methods of inferior oblique(IO)recession in V-pattern strabismus with inferior oblique overaction(IOOA).METHODS:Comparative randomized study was conducted consistin...AIM:To compare outcomes of conventional and Hangback methods of inferior oblique(IO)recession in V-pattern strabismus with inferior oblique overaction(IOOA).METHODS:Comparative randomized study was conducted consisting of 50 patients,age 6 to 35 y having V-pattern strabismus[>15 prism diopter(PD)]with IOOA.They were divided equally in two groups and underwent IO recession,group A by conventional method and group B by Hang-back method.Parameters evaluated were reduction in V-pattern and IOOA,shift in torsion,improvement in binocular status.Success was a residual V-pattern of less than 10 PD at 1 y of follow up.RESULTS:The mean V-pattern preoperatively and postoperatively at 1 y was 24±5.4 PD and 4.2±3.51 PD in group A and 23.44±6.44 PD and 5.76±3.8 PD in group B respectively.The mean reduction in V-pattern was 20±6.78 PD in group A and 18.2±5.48 PD in group B.The mean correction of IOOA was 18.48±3.13 PD in group A and 16±2.93 PD in group B.Mean shift in extorsion was 3.08±1.8 degree in group A and 3.72±2.14 degree in group B.CONCLUSION:Both the procedures achieve a significant and comparable reduction in V-pattern and IOOA.Hang-back recession being a landmark free surgery eliminates the need for intrascleral suturing thereby reducing the risk of scleral perforation with possible postoperative adjustment of muscle.It may be considered as a good alternative for IO recession in patients of V-pattern strabismus with mild to moderate amount of IOOA.展开更多
基金supported by a Fill in the Gap fellowship(Medical Faculty Freiburg)(to JDL)a Fritz Thyssen Stiftung grant,a European Stroke Research Foundation(ESRF)grant,a Wings for Life foundation grantthe DFG grants SCHA 1442/8-1,SCHA 1442/8-3,and SCHA 1442/9-1(to CS).
文摘Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the host microenvironment,which in turn affects the functionality of transplanted human neural stem/progenitor cells and potentially limits their benefits for neurorepair.However,the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood.Here,we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment.Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3.ID3-depleted human neural stem/progenitor cells,generated by CRISPR/Cas9-mediated genome editing,reduced astrocyte formation in response to astrogenic stimuli.Instead,ID3-depleted human neural stem/progenitor cells had a bipolar,immature glial progenitor cell phenotype.These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth.We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells,potentially enhancing their capacity to promote central nervous system repair.
文摘AIM:To evaluate functional outcome of sutureless scleral tunnel intraocular lens(SSTIOL)in children with crystalline lens subluxation of more than 7 clock hours.METHODS:A prospective interventional study was conducted consisting of 45 eyes of 44 children in age group 6-18 y having>7 clock hours of lens subluxation who underwent lensectomy-vitrectomy followed by SSTIOL implantation.Primary outcome was improvement in best corrected visual acuity(BCVA)and secondary outcomes were assessment of intraocular lens(IOL)tilt using ultrasound biomicroscopy(UBM),mean change in astigmatism at last follow-up of 1 y and associated complications.RESULTS:The mean preoperative and postoperative BCVA was 1.05±0.28 and 0.64±0.45(log MAR)respectively(P=0.001)at last follow-up.The mean astigmatism preoperatively and postoperatively was-4.17±2.69 D and-1.86±1.25 D respectively(P=0.011).Significant IOL tilt(>5 degrees)was present in 5 cases.The mean percentage endothelial loss was 3.65%±1.92%.The most serious complication encountered was retinal detachment seen in 2 cases.CONCLUSION:SSTIOL implantation provides efficient visual rehabilitation in children provided there is stringent case selection.We recommend caution in children having white-to-white distance>12 mm and presence of peripheral retinal degenerations.
文摘AIM:To compare outcomes of conventional and Hangback methods of inferior oblique(IO)recession in V-pattern strabismus with inferior oblique overaction(IOOA).METHODS:Comparative randomized study was conducted consisting of 50 patients,age 6 to 35 y having V-pattern strabismus[>15 prism diopter(PD)]with IOOA.They were divided equally in two groups and underwent IO recession,group A by conventional method and group B by Hang-back method.Parameters evaluated were reduction in V-pattern and IOOA,shift in torsion,improvement in binocular status.Success was a residual V-pattern of less than 10 PD at 1 y of follow up.RESULTS:The mean V-pattern preoperatively and postoperatively at 1 y was 24±5.4 PD and 4.2±3.51 PD in group A and 23.44±6.44 PD and 5.76±3.8 PD in group B respectively.The mean reduction in V-pattern was 20±6.78 PD in group A and 18.2±5.48 PD in group B.The mean correction of IOOA was 18.48±3.13 PD in group A and 16±2.93 PD in group B.Mean shift in extorsion was 3.08±1.8 degree in group A and 3.72±2.14 degree in group B.CONCLUSION:Both the procedures achieve a significant and comparable reduction in V-pattern and IOOA.Hang-back recession being a landmark free surgery eliminates the need for intrascleral suturing thereby reducing the risk of scleral perforation with possible postoperative adjustment of muscle.It may be considered as a good alternative for IO recession in patients of V-pattern strabismus with mild to moderate amount of IOOA.
