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Lycium barbarum glycopeptide(wolfberry extract)slows N-methyl-N-nitrosourea-induced degradation of photoreceptors 被引量:1
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作者 Qihang Kong Xiu Han +8 位作者 Haiyang Cheng Jiayu Liu Huijun Zhang Tangrong Dong Jiansu Chen Kwok-Fai So Xuesong Mi Ying Xu Shibo Tang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第10期2290-2298,共9页
Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photo... Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration. 展开更多
关键词 anti-inflammation inherited retinal diseases Lycium barbarum glycopeptide N-METHYL-N-NITROSOUREA OPSIN photoreceptor reactive gliosis retinal degeneration retinitis pigmentosa RHODOPSIN
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Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa
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作者 Sam Enayati Karen Chang +10 位作者 Anton Lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第11期2543-2552,共10页
Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on pho... Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion. 展开更多
关键词 bipolar cells electrical stimulation NEUROPROTECTION photoreceptor degeneration RETINA retinal explants retinitis pigmentosa transcorneal electrical stimulation WAVEFORM
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Restoration of outer segments of foveal photoreceptors after resolution of malignant hypertensive retinopathy
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作者 Xiao-Qiang Liu Xin-Rui Gao +3 位作者 Ding Xu Chong Xu Li-Ning Cao Fang Wang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2012年第6期776-778,共3页
Dear Sir,I am Dr. Xiao-Qiang Liu, from the Department of Ophthalmology, Shanghai Tenth People’s Hospital,Tongji University School of Medicine, Shanghai, China. I write to report a case of malignant hypertensive retin... Dear Sir,I am Dr. Xiao-Qiang Liu, from the Department of Ophthalmology, Shanghai Tenth People’s Hospital,Tongji University School of Medicine, Shanghai, China. I write to report a case of malignant hypertensive retinopathy demonstrated by spectral domain optical coherence 展开更多
关键词 line Restoration of outer segments of foveal photoreceptors after resolution of malignant hypertensive retinopathy OS
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Differentiation potential of human adipose tissue derived stem cells into photoreceptors through explants culture and enzyme methods 被引量:3
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作者 Wei-Wei Xu Li Huang +5 位作者 Kelvin K.L.Chong Doreen S.Y.Leung Benjamin EL.Li Zheng-Qin Yin Yi-Fei Huang Chi Pui Pang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2017年第1期23-29,共7页
AIM: To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells (ADSCs) generated by enzyme (EN) and explant (EX) culture methods.METHODS: We investig... AIM: To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells (ADSCs) generated by enzyme (EN) and explant (EX) culture methods.METHODS: We investigated potentials of human orbital ADSCs to differentiate into photoreceptors through EN and EX culture methods. EN and EX orbital ADSCs were obtained from the same donor during rehabilitative orbital decompression, and then were subject to a 3-step induction using Noggin, DKK-1, IGF-1 and b-FGF at different time points for 38d. Stem cell, eye-field and photoreceptor-related gene and protein markers were measured by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescent (IMF) staining.RESULTS: Both EX and EN orbital ADSCs expressed CD133, a marker of cell differentiation. Moreover, PAX6 and rhodopsin, markers of the retinal progenitor cells, were detected from EX and EN orbital ADSCs. In EX orbital ADSCs, PAX6 mRNA was detected on the 17th day and then the rhodopsin mRNA was detected on the 24th day. In contrast, the EN orbital ADSCs expressed PAX6 and rhodopsin mRNA on the 31st day. EX orbital ADSCs expressed rhodopsin protein on the 24th day, while EN orbital ADSCs expressed rhodopsin protein on the 31st day. CONCLUSION: Orbital ADSCs isolated by direct explants culture show earlier and stronger expressions of markers towards eye field and retinal photoreceptor differentiation than those generated by conventional EN method. 展开更多
关键词 photoreceptor cells cell differentiation adultstem cells tissue engineering explants culture enzymaticdigestion
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Mode-Field-Diameter and the Coupling Loss between Inner and Outer Segment of Photoreceptors 被引量:1
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作者 Anhui Liang Leiting Hu Zhimin Liang 《Optics and Photonics Journal》 2015年第4期151-160,共10页
The characteristics of optical waveguide of human photoreceptors play important roles in vision. The mode-field-diameter (MFD) is a very important parameter of a single-mode waveguide, and it is related to many import... The characteristics of optical waveguide of human photoreceptors play important roles in vision. The mode-field-diameter (MFD) is a very important parameter of a single-mode waveguide, and it is related to many important optical characteristics of a single-mode waveguide. Here we show that MFDs of outer segments of human foveal cones are close to the minimum values at their geometric diameter for outer segments of foveal cones. Small MFD of outer segment is important for eyes to have high spatial resolution and low interaction between neighboring cones. We propose that the ellipsoids of foveal cones act as spot size converters to reduce the coupling losses between myoids and outer segments. 展开更多
关键词 PHOTORECEPTOR Mode-Field-Diameter Spot Size Converter Coupling
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The GmSTF1/2–GmBBX4 negative feedback loop acts downstream of blue-light photoreceptors to regulate isoflavonoid biosynthesis in soybean
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作者 Zhaoqing Song Fengyue Zhao +10 位作者 Li Chu Huan Lin Yuntao Xiao Zheng Fang Xuncheng Wang Jie Dong Xiangguang Lyu Deyue Yu Bin Liu Junyi Gai Dongqing Xu 《Plant Communications》 SCIE CSCD 2024年第2期198-214,共17页
Isoflavonoids,secondary metabolites derived from the phenylalanine pathway,are predominantly bio-synthesized in legumes,especially soybean(Glycine max).They are not only essential for plant responses to biotic and abi... Isoflavonoids,secondary metabolites derived from the phenylalanine pathway,are predominantly bio-synthesized in legumes,especially soybean(Glycine max).They are not only essential for plant responses to biotic and abiotic stresses but also beneficial to human health.In this study,we report that light signaling controls isoflavonoid biosynthesis in soybean.Blue-light photoreceptors(GmCRY1s,GmCRY2s,GmPHOT1s,and GmPHOT2s)and the transcription factors GmSTF1 and GmSTF2 promote isoflavonoid accumulation,whereas the E3 ubiquitin ligase GmCOP1b negatively regulates isoflavonoid biosynthesis.GmPHOT1s and GmPHOT2s stabilize GmSTF1/2,whereas GmCOP1b promotes the degradation of these two proteins in soybean.GmSTF1/2 regulate the expression of approximately 27.9%of the genes involved in soybean isoflavonoid biosynthesis,including GmPAL2.1,GmPAL2.3,and GmUGT2.They also repress the expression of GmBBX4,a negative regulator of isoflavonoid biosynthesis in soybean.In addition,GmBBX4 physically interacts with GmSTF1 and GmSTF2 to inhibit their transcriptional activation activity toward target genes related to isoflavonoid biosynthesis.Thus,GmSTF1/2 and GmBBX4 form a negative feedback loop that acts downstream of photoreceptors in the regulation of isoflavonoid biosynthesis.Our study provides novel insights into the control of isoflavonoid biosynthesis by light signaling in soybean and will contribute to the breeding of soybean cultivars with high isoflavonoid content through genetic and metabolic engineering. 展开更多
关键词 PHOTORECEPTOR light signaling ISOFLAVONOID GmSTF GmBBX4 SOYBEAN
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Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy
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作者 Samuel Abokyi Dennis Yan-yin Tse 《Neural Regeneration Research》 SCIE CAS 2025年第2期366-377,共12页
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu... Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects. 展开更多
关键词 age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma NEUROMODULATION PHAGOCYTOSIS photoreceptor outer segment degradation retinal aging transcription factor EB
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Control of Plant Growth and Defense by Photoreceptors:From Mechanisms to Opportunities in Agriculture 被引量:6
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作者 Ronald Pierik Carlos L.Ballare 《Molecular Plant》 SCIE CAS CSCD 2021年第1期61-76,共16页
Plants detect and respond to the proximity of competitors using light signals perceived by photoreceptor proteins.A low ratio of red to far-red radiation(R:FR ratio)is a key signal of competition that is sensed by the... Plants detect and respond to the proximity of competitors using light signals perceived by photoreceptor proteins.A low ratio of red to far-red radiation(R:FR ratio)is a key signal of competition that is sensed by the photoreceptor phytochrome B(phyB).Low R:FR ratios increase the synthesis of growth-related hormones,including auxin and gibberellins,promoting stem elongation and other shade-avoidance responses.Other photoreceptors that help plants to optimize their developmental configuration and resource allocation patterns in the canopy include blue light photoreceptors,such as cryptochromes and phototropins,and UV receptors,such as UVR8.All photoreceptors act by directly or indirectly controlling the activity of two major regulatory nodes for growth and development:the COP1/SPA ubiquitin E3 ligase complex and the PIF transcription factors.phyB is also an important modulator of hormonal pathways that regulate plant defense against herbivores and pathogens,including the jasmonic acid signaling pathway,In this Perspective,we discuss recent advances on the studies of the mechanisms that link photoreceptors with growth and defense.Understanding these mechanisms is important to provide a functional platform for breeding programs aimed at improving plant productivity,stress tolerance,and crop health in species of agronomic interest,and to manipulate the light environments in protected agriculture. 展开更多
关键词 PHOTORECEPTOR PHYTOCHROME JASMONATE growth-defense trade-off SHADE avoidance immunity
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Taurine: a promising nutraceutic in the prevention of retinal degeneration 被引量:2
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作者 Diego García-Ayuso Johnny Di Pierdomenico +3 位作者 Ana Martínez-Vacas Manuel Vidal-Sanz Serge Picaud María PVillegas-Pérez 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第3期606-610,共5页
Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenanc... Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical. 展开更多
关键词 amino acid ANTI-INFLAMMATORY ANTIOXIDANT gamma-aminobutyric acid NUTRACEUTICAL photoreceptor degeneration RETINA retinitis pigmentosa TAURINE
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Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure
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作者 Shaojun Wang Siti Tong +5 位作者 Xin Jin Na Li Pingxiu Dang Yang Sui Ying Liu Dajiang Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第11期2522-2531,共10页
High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat ... High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies. 展开更多
关键词 APOPTOSIS axon degeneration high intraocular pressure MICROGLIA ocular hypertension photoreceptor cells RETINA retinal degeneration retinal ganglion cells single-cell RNA sequencing
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Protective effects of CY-09 and astaxanthin on NaIO_(3)-induced photoreceptor inflammation via the NLRP3/autophagy pathway
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作者 Xiao-Li Wang Yun-Xia Gao +1 位作者 Qiong-Zhen Yuan Ming Zhang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第7期1217-1231,共15页
AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY... AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST groups.Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western blotting.Retinal pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST successively.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay.Apoptosis was analyzed by flow cytometry.Changes in autophagosome morphology were observed by transmission electron microscopy.Quantitative polymerase chain reaction(qPCR)was used to detect NLRP3 and caspase-1.NLRP3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western blotting.IL-1βand IL-18 were measured by ELISA.RESULTS:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited autophagy.Compared with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo.CY-09 and AST may protect retina from inflammatory injury. 展开更多
关键词 CY-09 ASTAXANTHIN retinal degeneration photoreceptor cells INFLAMMATION NLRP3
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Retinitis pigmentosa and stem cell therapy
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作者 Xin-Ya Qi Chen-Hui Mi +2 位作者 De-Rui Cao Xie-Qun Chen Peng Zhang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第7期1363-1369,共7页
Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)cells.Its main clinical manifestations include night blindness and... Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)cells.Its main clinical manifestations include night blindness and progressive loss of peripheral vision,making it a prevalent debilitating eye disease that significantly impacts patients’quality of life.RP exhibits significant phenotypic and genetic heterogeneity.For instance,numerous abnormal genes are implicated in RP,resulting in varying clinical presentations,disease progression rates,and pathological characteristics among different patients.Consequently,gene therapy for RP poses challenges due to these complexities.However,stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells.In recent years,a large number of animal experiments and clinical trials based on stem cell transplantation attempts,especially cord blood mesenchymal stem cell(MSC)transplantation and bone marrow-derived MSC transplantation,have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye.However,stem cell therapy also has certain limitations,such as the fact that RP patients may involve multiple types of retinal cytopathia,which brings great challenges to stem cell transplantation therapy,and further research is needed to solve various problems faced by this approach in the clinic.Through comprehensive analysis of the etiology and histopathological changes associated with RP,this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials,while also highlighting the existing limitations that warrant further investigation. 展开更多
关键词 retinitis pigmentosa PHOTORECEPTOR stem cell therapy
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Circadian regulation of Limulus visual functions:A role for octopamine and cAMP 被引量:3
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作者 Jasbir S.DALAL Barbara-Anne BATTELLE 《Current Zoology》 SCIE CAS CSCD 北大核心 2010年第5期518-536,共19页
The purpose of this contribution is to review our current understanding of the source and biochemistry of the circadian efferent input to the eyes of the American horseshoe crab Limuluspolyphemus and the impact of thi... The purpose of this contribution is to review our current understanding of the source and biochemistry of the circadian efferent input to the eyes of the American horseshoe crab Limuluspolyphemus and the impact of this input on the structure, physiology and biochemistry of Limulus eyes. Special emphasis is given to the role of the biogenic amine octopamine and bio- chemical cascades it activates in the eyes. In addition to reviewing published data, we present new data showing that octopamine elevates cAMP levels in Limulus lateral eyes, and we partially characterize the pharmacology of the receptors involved in this response. We also present new data showing that octopamine regulates gene expression in Limulus lateral eyes by activating a cAMP cascade 展开更多
关键词 Horseshoe crab Circadian rhythms Oetopamine photoreceptors Substance P ARRESTIN
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The future of retinal gene therapy: evolving from subretinal to intravitreal vector delivery 被引量:3
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作者 Maya Ross Ron Ofri 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第9期1751-1759,共9页
Inherited retinal degenerations are a leading and untreatbale cause of blindness, and as such they are targets for gene therapy. Numerous gene therapy treatments have progressed from laboratory research to clinical tr... Inherited retinal degenerations are a leading and untreatbale cause of blindness, and as such they are targets for gene therapy. Numerous gene therapy treatments have progressed from laboratory research to clinical trails, and a pioneering gene therapy received the first ever FDA approval for treating patients. However, currently retinal gene therapy mostly involves subretinal injection of the therapeutic agent, which treats a limited area, entails retinal detachment and other potential complications, and requires general anesthesia with consequent risks, costs and prolonged recovery. Therefore there is great impetus to develop safer, less invasive and cheapter methods of gene delivery. A promising method is intravitreal injection, that does not cause retinal detachment, can lead to pan-retinal transduction and can be performed under local anesthesia in outpatient clinics. Intravitreally-injected vectors face several obstacles. First, the vector is diluted by the vitreous and has to overcome a long diffusion distance to the target cells. Second, the vector is exposed to the host's immune response, risking neutralization by pre-existing antibodies and triggering a stronger immune response to the injection. Third, the vector has to cross the inner limiting membrane which is both a physical and a biological barrier as it contains binding sites that could cause the vector's sequestration. Finally, in the target cell the vector is prone to proteasome degradation before delivering the transgene to the nucleus. Strategies to overcome these obstacles include modifications of the viral capsid, through rational design or directed evolution, which allow resistance to the immune system, enhancement of penetration through the inner limiting membrane or reduced degradation by intracellular proteasomes. Furthermore, physical and chemical manipulations of the inner limiting membrane and vitreous aim to improve vector penetration. Finally, compact non-viral vectors that can overcome the immunological, physical and anatomical and barriers have been developed. This paper reviews ongoing efforts to develop novel, safe and efficacious methods for intravitreal delivery of therapeutic genes for inherited retinal degenerations. To date, the most promising results are achieved in rodents with robust, pan-retinal transduction following intravitreal delivery. Trials in larger animal models demonstrate transduction mostly of inner retinal layers. Despite ongoing efforts, currently no intravitreally-injected vector has demonstrated outer retinal transduction efficacy comparable to that of subretinal delivery. Further work is warranted to test promising new viral and non-viral vectors on large animal models of inherited retinal degenerations. Positive results will pave the way to development of the next generation of treatments for inherited retinal degeneration. 展开更多
关键词 adeno-associated virus animal model BLINDNESS gene therapy inner limiting membrane photoreceptors RETINA retinitis pigmentosa VITREOUS
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Intravitreal stem cell paracrine properties as a potential neuroprotective therapy for retinal photoreceptor neurodegenerative diseases 被引量:3
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作者 Kevin Puertas-Neyra Ricardo Usategui-Martín +1 位作者 Rosa MCoco Ivan Fernandez-Bueno 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第9期1631-1638,共8页
Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age... Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs. 展开更多
关键词 clinical trials growth factors intraocular injection intravitreal injection neuroprotection paracrine properties photoreceptors preclinical models retinal diseases stem cells
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Cell transplantation to replace retinal ganglion cells faces challenges-the Switchboard Dilemma 被引量:3
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作者 Yuan Liu Richard K.Lee 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第6期1138-1143,共6页
The mammalian retina displays incomplete intrinsic regenerative capacities;therefore,retina degeneration is a major cause of irreversible blindness such as glaucoma,agerelated macular degeneration and diabetic retinop... The mammalian retina displays incomplete intrinsic regenerative capacities;therefore,retina degeneration is a major cause of irreversible blindness such as glaucoma,agerelated macular degeneration and diabetic retinopathy.These diseases lead to the loss of retinal cells and serious vision loss in the late stage.Stem cell transplantation is a great promising novel treatment for these incurable retinal degenerative diseases and represents an exciting area of regenerative neurotherapy.Several suitable stem cell sources for transplantation including human embryonic stem cells,induced pluripotent stem cells and adult stem cells have been identified as promising target populations.However,the retina is an elegant neuronal complex composed of various types of cells with different functions.The replacement of these different types of cells by transplantation should be addressed separately.So far,retinal pigment epithelium transplantation has achieved the most advanced stage of clinical trials,while transplantation of retinal neurons such as retinal ganglion cells and photoreceptors has been mostly studied in pre-clinical animal models.In this review,we opine on the key problems that need to be addressed before stem cells transplantation,especially for replacing injured retinal ganglion cells,may be used practically for treatment.A key problem we have called the Switchboard Dilemma is a major block to have functional retinal ganglion cell replacement.We use the public switchboard telephone network as an example to illustrate different difficulties for replacing damaged components in the retina that allow for visual signaling.Retinal ganglion cell transplantation is confronted by significant hurdles,because retinal ganglion cells receive signals from different interneurons,integrate and send signals to the correct targets of the visual system,which functions similar to the switchboard in a telephone network-therefore the Switchboard Dilemma. 展开更多
关键词 cell transplantation optic nerve regeneration photoreceptors retina degeneration retinal ganglion cells stem cells
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Neural and Müller glial adaptation of the retina to photoreceptor degeneration 被引量:2
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作者 Henri O.Leinonen Edward Bull Zhongjie Fu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第4期701-707,共7页
The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors,which leads to progressive loss of vision.The inner re... The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors,which leads to progressive loss of vision.The inner retina,including second-and third-order retinal neurons,also shows aberrant structural changes at all stages of degeneration.Müller glia,the major glial cells maintain retinal homeostasis,activating and rearranging immediately in response to photoreceptor stress.These phenomena are collectively known as retinal remodeling and are anatomically well described,but their impact on visual function is less well characterized.Retinal remodeling has traditionally been considered a detrimental chain of events that decreases visual function.However,emerging evidence from functional assays suggests that remodeling could also be a part of a survival mechanism wherein the inner retina responds plastically to outer retinal degeneration.The visual system’s first synapses between the photoreceptors and bipolar cells undergo rewiring and functionally compensate to maintain normal signal output to the brain.Distinct classes of retinal ganglion cells remain even after the massive loss of photoreceptors.Müller glia possess the regenerative potential for retinal recovery and possibly exert adaptive transcriptional changes in response to neuronal loss.These types of homeostatic changes could potentially explain the well-maintained visual function observed in patients with inherited retinal degenerative diseases who display prominent anatomic retinal pathology.This review will focus on our current understanding of retinal neuronal and Müller glial adaptation for the potential preservation of retinal activity during photoreceptor degeneration.Targeting retinal self-compensatory responses could help generate universal strategies to delay sensory disease progression. 展开更多
关键词 bipolar cells ELECTRORETINOGRAPHY Müller glia photoreceptors plasticity retinal degeneration retinal neuron retinal remodeling retinal ganglion cells
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Light quality and temperature effects on antirrhinum growth and development 被引量:2
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作者 KHATTAK Abdul Mateen PEARSON Simon 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2005年第2期119-124,共6页
An experiment was carried out to examine the effects of light quality on the growth and development of antirrhinum under three different temperatures 19℃, 24℃ and 27℃ in glasshouses. Five different colour filters (... An experiment was carried out to examine the effects of light quality on the growth and development of antirrhinum under three different temperatures 19℃, 24℃ and 27℃ in glasshouses. Five different colour filters (i.e. 'Red absorbing', 'Blue absorbing', 'Blue and Red absorbing' and two 'partially Blue absorbing' materials) were tested, with one clear polythene as a control. Plant height, internode length and leaf area were significantly affected by the spectral filters as well as the temperature.Analysis of color filter's effect on presumed photoreceptors to exist indicated that antirrhinum plant height was regulated by the action of a blue acting photoreceptor (BAP) and not the phytochrome. There was no evidence for an effect ofphytochrome or BAP on time to flowering, however, increasing temperature levels effectively decreased the time to flowering. To predict the effects of different spectral qualities and temperature, simple models were created from data on plant height, internode length and time to flowering. These models were then applied to simulate the potential benefits of spectral filters and temperature in manipulation of growth control and flowering in antirrhinum. 展开更多
关键词 ANTIRRHINUM Light quality TEMPERATURE Spectral filters photoreceptors
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The neuroprotective role of Wnt signaling in the retina 被引量:2
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作者 Stefan Kassumeh Gregor R.Weber +2 位作者 Matthias Nobl Siegfried G.Priglinger Andreas Ohlmann 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第8期1524-1528,共5页
The canonical Wnt/β-catenin signaling pathway has been shown to play a major role during embryonic development and maturation of the central nervous system including the retina. It has a significant impact on retinal... The canonical Wnt/β-catenin signaling pathway has been shown to play a major role during embryonic development and maturation of the central nervous system including the retina. It has a significant impact on retinal vessel formation and maturation, as well as on the establishment of synaptic structures and neuronal function in the central nervous system. Mutations in components of the Wnt/β-catenin signaling cascade may lead to severe retinal diseases, while dysregulation of Wnt signaling can contribute to disease progression. Apart from the angiogenic role of Wnt/β-catenin signaling, research in the last decades leads to the theory of a protective effect of Wnt/β-catenin signaling on damaged neurons. In this review, we focus on the neuroprotective properties of the Wnt/β-catenin pathway as well as its downstream signaling in the retina. 展开更多
关键词 apoptosis β-catenin leukemia inhibitory factor Müller cells NEURODEGENERATION NEUROPROTECTION Norrin photoreceptors RETINA retinal ganglion cells WNT
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Multicolor pattern scan laser for diabetic retinopathy with cataract 被引量:2
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作者 Takao Hirano Yasuhiro Iesato Toshinori Murata 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2014年第4期673-676,共4页
· AIM: To evaluate the ability of various laser wavelengths in delivering sufficient burns to the retina in eyes with cataract using a new multicolor pattern scan laser with green(532 nm), yellow(577 nm), and red... · AIM: To evaluate the ability of various laser wavelengths in delivering sufficient burns to the retina in eyes with cataract using a new multicolor pattern scan laser with green(532 nm), yellow(577 nm), and red(647 nm)lasers.·METHODS: The relationship between the Emery-Little(EL) degree of cataract severity and the laser wavelength required to deliver adequate burns was investigated in102 diabetic eyes. Treatment time, total number of laser shots, and intra-operative pain were assessed as well.·RESULTS: All EL-1 grade eyes and 50% of EL-2 eyes were successfully treated with the green laser, while 50%of EL-2 eyes, 96% of EL-3 eyes, and 50% of EL-4 eyes required the yellow laser. The red laser was effective in the remaining 4% of EL-3 and 50% of EL-4 eyes.·CONCLUSION: Longer wavelength lasers are more effective in delivering laser burns through cataract when we use a multicolor pattern scan laser system. 展开更多
关键词 diabetic macular edema PHOTOCOAGULATION retinal hemorrhage PAIN photoreceptors
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