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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National clinical research center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and Stem Cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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Women in visual neural regeneration research

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Neural Regeneration research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David J.Calkins Vanderbilt eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical research and data from the major professional organization for eye and vision research,the Association for research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei Henan eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National clinical research center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang Department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National clinical research center for eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

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Neural Regeneration research 2025年第2期20卷 366-377页

作者： Samuel Abokyi Dennis Yan-yin Tse School of Optometry The Hong Kong Polytechnic UniversityKowloonHong Kong Special Administrative RegionChina research center for SHARP Vision The Hong Kong Polytechnic UniversityKowloonHong Kong Special Administrative RegionChina center for eye and Vision research Sha TinHong Kong Special Administrative RegionChina

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 *** comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor *** 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 *** review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal *** 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 *** 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 ***,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and *** 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 *** cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering pro

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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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for research of Acupuncture Treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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Neural Regeneration research 2025年第10期20卷 2741-2757页

作者： Qianzi Jin Suyu Wang Yujia Yao Qin Jiang Keran Li Department of Ophthalmology The Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina The Fourth School of clinical Medicine Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts ***,the specific pathogenesis remains unclear,and effective early treatment options are consequently *** microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a *** intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other *** dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many *** recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the ***,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s ***,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular ***,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable *** such,the intestinal flora may play an important role in age-related macular *** the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic ***,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular ***-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the inte

关键词： age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora metabolite microecology neurodegenerative disease

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Effect of cholesterol metabolism on hepatolithiasis

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World Journal of Gastroenterology 2025年第1期31卷 157-162页

作者： Lin Zheng Zi-Yu Ye Jun-Ji Ma Department of Gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesNo.215 Heping West RoadShijiazhuang 050000Hebei ProvinceChina

Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after *** metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of ***,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after *** dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating *** article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.

关键词： Hepatolithiasis Cholesterol metabolism High-fat diet 3-hydroxy-3-methylglutaryl-coenzyme A reductase Interlobular bile duct

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