Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral g...Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).展开更多
We present the first demonstration of shot-noise limited supercontinuum-based spectral domain optical coherence tomography(SD-OCT)with an axial resolution of 5.9μm at a center wavelength of 1370 nm.Current superconti...We present the first demonstration of shot-noise limited supercontinuum-based spectral domain optical coherence tomography(SD-OCT)with an axial resolution of 5.9μm at a center wavelength of 1370 nm.Current supercontinuumbased SD-OCT systems cannot be operated in the shot-noise limited detection regime because of severe pulse-topulse relative intensity noise of the supercontinuum source.To overcome this disadvantage,we have developed a low-noise supercontinuum source based on an all-normal dispersion(ANDi)fiber,pumped by a femtosecond laser.The noise performance of our 90 MHz ANDi fiber-based supercontinuum source is compared to that of two commercial sources operating at 80 and 320 MHz repetition rate.We show that the low-noise of the ANDi fiber-based supercontinuum source improves the OCT images significantly in terms of both higher contrast,better sensitivity,and improved penetration.From SD-OCT imaging of skin,retina,and multilayer stacks we conclude that supercontinuumbased SD-OCT can enter the domain of shot-noise limited detection.展开更多
基金MT was funded by the Leistungsorientierte Mittelvergabe(LOM)scholarship offered by the medical faculty of Magdeburg and the Deutscher Akademischer Austauschdienst(DAAD).
文摘Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).
基金European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No.722380(the project SUPUVIR)Innovation Fund Denmark under the project J.No.4107-00011A(the project ShapeOCT)Det Frie Forskningsråd(DFF)under the project No.LOISE-4184-00532B(the project LOISE).
文摘We present the first demonstration of shot-noise limited supercontinuum-based spectral domain optical coherence tomography(SD-OCT)with an axial resolution of 5.9μm at a center wavelength of 1370 nm.Current supercontinuumbased SD-OCT systems cannot be operated in the shot-noise limited detection regime because of severe pulse-topulse relative intensity noise of the supercontinuum source.To overcome this disadvantage,we have developed a low-noise supercontinuum source based on an all-normal dispersion(ANDi)fiber,pumped by a femtosecond laser.The noise performance of our 90 MHz ANDi fiber-based supercontinuum source is compared to that of two commercial sources operating at 80 and 320 MHz repetition rate.We show that the low-noise of the ANDi fiber-based supercontinuum source improves the OCT images significantly in terms of both higher contrast,better sensitivity,and improved penetration.From SD-OCT imaging of skin,retina,and multilayer stacks we conclude that supercontinuumbased SD-OCT can enter the domain of shot-noise limited detection.
