Clinically,a large proportion of glaucoma patients undergo repeated intraocular pressure(IOP)spike(Spike IOP)attacks during their sleep,which may facilitate retinopathy.In this study,we established a mouse model of re...Clinically,a large proportion of glaucoma patients undergo repeated intraocular pressure(IOP)spike(Spike IOP)attacks during their sleep,which may facilitate retinopathy.In this study,we established a mouse model of repeated transient Spike IOP to investigate the direct damage to the retina following Spike IOP attacks,and elucidated the underlying molecular mechanism.We analyzed the changes in the number of retinal ganglion cells(RGCs)via immunofluorescence.Thereafter,we detected retinal cell apoptosis via terminal deoxynucleotidyl transferase deoxyuridine triphosphate(d UTP)nick-end labeling(TUNEL)staining,and performed RNA sequencing(RNA-seq)to reveal the underlying molecular mechanism.Finally,we validated the expression of key molecules in the endoplasmic reticulum(ER)stress pathway using quantitative real-time polymerase chain reaction(q RT-PCR)and western blot analysis.Results revealed a time-dependent RGC loss in Spike IOP,evidenced by a reduction in the number of Brn3 a-positive RGCs in experimental eyes following a 7-d continuous treatment with Spike IOP.In addition,TUNEL staining indicated that apoptosis of retinal cells started in the outer nuclear layer(ONL),and then spread to the ganglion cell layer(GCL)with time.RNA-seq analysis revealed that ER stress might be involved in Spike IOP-induced retinal injury.This result was corroborated by western blot,which revealed upregulation of ER stress-related proteins including binding immunoglobulin protein/glucose-regulated protein 78(Bi P/GRP78),phosphorylated inositolrequiring enzyme 1(p-IRE1),unspliced X-box-binding protein 1(XBP1-u),spliced X-box-binding protein 1(XBP1-s),phosphorylated c-Jun N-terminal kinase(p-JNK),C/EBP-homologous protein(CHOP),and B-cell lymphoma 2(Bcl-2)-associated X protein(Bax).These findings indicate that repeated IOP transients are detrimental to the retina,while ER stress plays an important role in retinal cell apoptosis in this situation.Notably,repeated Spike IOP among glaucoma patients is a crucial factor for progressive retino展开更多
Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases.Establishing biological retinal models and simulating how the biological retina convert incoming light...Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases.Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue.Some retinal models have been presented,ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena.However,Most of these focus on stimulus image compression,edge detection and reconstruction,but do not generate spike trains corresponding to visual image.In this study,based on stateof-the-art retinal physiological mechanism,including effective visual information extraction,static nonlinear rectification of biological systems and neurons Poisson coding,a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward,which integrates both anatomic connections and functional computations of retina.Using MATLAB software,spike trains corresponding to stimulus image were numerically computed by four steps：linear spatiotemporal filtering,static nonlinear rectification,radial sampling and then Poisson spike generation.The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina,which is helpful in developing artificial retina for the retinally blind.展开更多
基金supported by the Guangzhou Science and Technology Plan Project(Nos.201803040020,201903010065202102021099)+1 种基金the Guangdong Natural Science Foundation(No.2020A151501168)the Research Funds of the State Key Laboratory of Ophthalmology(No.PT1001022),China。
文摘Clinically,a large proportion of glaucoma patients undergo repeated intraocular pressure(IOP)spike(Spike IOP)attacks during their sleep,which may facilitate retinopathy.In this study,we established a mouse model of repeated transient Spike IOP to investigate the direct damage to the retina following Spike IOP attacks,and elucidated the underlying molecular mechanism.We analyzed the changes in the number of retinal ganglion cells(RGCs)via immunofluorescence.Thereafter,we detected retinal cell apoptosis via terminal deoxynucleotidyl transferase deoxyuridine triphosphate(d UTP)nick-end labeling(TUNEL)staining,and performed RNA sequencing(RNA-seq)to reveal the underlying molecular mechanism.Finally,we validated the expression of key molecules in the endoplasmic reticulum(ER)stress pathway using quantitative real-time polymerase chain reaction(q RT-PCR)and western blot analysis.Results revealed a time-dependent RGC loss in Spike IOP,evidenced by a reduction in the number of Brn3 a-positive RGCs in experimental eyes following a 7-d continuous treatment with Spike IOP.In addition,TUNEL staining indicated that apoptosis of retinal cells started in the outer nuclear layer(ONL),and then spread to the ganglion cell layer(GCL)with time.RNA-seq analysis revealed that ER stress might be involved in Spike IOP-induced retinal injury.This result was corroborated by western blot,which revealed upregulation of ER stress-related proteins including binding immunoglobulin protein/glucose-regulated protein 78(Bi P/GRP78),phosphorylated inositolrequiring enzyme 1(p-IRE1),unspliced X-box-binding protein 1(XBP1-u),spliced X-box-binding protein 1(XBP1-s),phosphorylated c-Jun N-terminal kinase(p-JNK),C/EBP-homologous protein(CHOP),and B-cell lymphoma 2(Bcl-2)-associated X protein(Bax).These findings indicate that repeated IOP transients are detrimental to the retina,while ER stress plays an important role in retinal cell apoptosis in this situation.Notably,repeated Spike IOP among glaucoma patients is a crucial factor for progressive retino
基金supported by the National Natural Science Foundation of China,No.30870649the National Program on Key Basic Research Project of China (973 Program),No.2005CB724302
文摘Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases.Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue.Some retinal models have been presented,ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena.However,Most of these focus on stimulus image compression,edge detection and reconstruction,but do not generate spike trains corresponding to visual image.In this study,based on stateof-the-art retinal physiological mechanism,including effective visual information extraction,static nonlinear rectification of biological systems and neurons Poisson coding,a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward,which integrates both anatomic connections and functional computations of retina.Using MATLAB software,spike trains corresponding to stimulus image were numerically computed by four steps：linear spatiotemporal filtering,static nonlinear rectification,radial sampling and then Poisson spike generation.The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina,which is helpful in developing artificial retina for the retinally blind.
