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The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

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Neural Regeneration Research 2025年第11期20卷 3211-3212页

作者： Sara Mazzoleni Marta Busnelli Silvia Bassani CNR Institute of Neuroscience Vedano al LambroItaly NeuroMi Milan center for Neuroscience MilanItaly

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive *** seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

关键词： epilepsy function system

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

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Neural Regeneration Research 2025年第3期20卷 900-912页

作者： Baoqi Hu Rui Wang Hanyue Zhang Xiou Wang Sijia Zhou Bo Ma Yan Luan Xin Wang Xinlin Chen Zhichao Zhang Qianyan Kang Department of ophthalmology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of ophthalmology The First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina Institute of Neurobiology Xi’an Jiaotong University Health Science CenterXi’anShaanxi ProvinceChina

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell ***,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development ***,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo *** this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in ***,we used SOX2 and PAX6 immunostaining to identify retinal progenitor *** then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,***-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between ***,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,*** timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant *** study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina *** findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

关键词： bipolar cells differentiation in vivo microglia Müller glia organotypic retinal explant culture postnatal retina development proliferation retinal progenitor cells

Revealing and predicting the long-term biomechanical response of orthokeratology by developing a patient-specific computational model

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 156-168页

作者： Yifeng Li Zhuoran Yang Ziming Yan Huibin Shi Zhanli Liu Kaijie Wang Department of Engineering Mechanics School of Aerospace Engineering Tsinghua University Beijing Tongren Eye center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Lab

Orthokeratology(OK) is widely used for effective myopia correction and control. However, the incomplete understanding of its biomechanical mechanisms makes OK lens fitting rely heavily on clinician judgment, complicating accurate predictions of treatment outcomes. In this paper, we performed clinical experiments and numerical analysis to study corneal deformation modes and long-term changes in central corneal thickness. Clinical experiments were conducted on 194 Chinese myopic patients under OK treatment for 3 months. Based on the experimental data, a patient-specific computational biomechanical model for OK was established and validated. Specifically, the anisotropic mechanical properties of the cornea were incorporated into the model to describe the significant difference between its shear modulus(29.5 kPa) and tensile modulus(768.4 kPa). Additionally, a viscohyperelastic material model with a prolonged corneal relaxation time of 5.6 h was developed to capture the long-term deformation response. The results show that corneal thickness reduction in OK is primarily due to out-of-plane shear deformation,influenced by the cornea's low shear resistance. Modeling the extended corneal relaxation time is crucial for predicting long-term biomechanical responses. The computational model effectively captures long-term changes in central corneal thickness, potentially improving OK lens fitting accuracy.

关键词： orthokeratology computational biomechanical model long-term viscoelasticity myopia correction

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

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.P.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

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

Apolipoprotein A-I binding protein-mediated neuroprotection in glaucomatous neuroinflammation and neurodegeneration

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Neural Regeneration Research 2025年第5期20卷 1414-1415页

作者： Sinwoo Hwang Seunghwan Choi Soo-Ho Choi Keun-Young Kim Yury I.Miller Won-Kyu Ju Hamilton Glaucoma center and Shiley Eye Institute The Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCAUSA Department of Medicine University of California San DiegoLa JollaCAUSA National center for Microscopy and Imaging Research Department of NeurosciencesUniversity of California San DiegoLa JollaCAUSA

Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs *** to the aging population,it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more *** primarily contributes to optic nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs),subsequently leading to vision impairment.

关键词： irreversible pass primarily

Philippine retinoblastoma initiative multi-eye center study 2010-2020

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International Journal of ophthalmology(English edition) 2024年第1期17卷 144-156页

作者： Roland Joseph D.Tan Gary John V.Mercado Patricia E.Cabrera Paulita Pamela P.Astudillo Rolando Enrique D.Domingo Josept Mari S.Poblete Charmaine Grace M.Cabebe Adriel Vincent R.Te Melissa Anne S.Gonzales Jocelyn G.Sy Beltran alexis A.Aclan Jayson T.So Fatima G.Regala Kimberley Amanda K.Comia Josemaria M.Castro Mara Augustine S.Galang aldous Dominic C.Cabanlas Benedicto Juan E.Aguilar Gabrielle S.Evangelista Jo Michael Maniwan Andrei P.Martin Calvin Y.Martinez John alfred H.Lim Rena Ivy Bascuna Rachel M.Ng Kevin B.Agsaoay Kris Zanna A.Acluba-Arao Ellaine Rose V.Apostol Beatriz M.Prieto Department of ophthalmology and Visual Sciences Philippine General HospitalManila 1000Philippines Department of ophthalmology Baguio General Hospital and Medical CenterBaguio City 2600Philippines Department of ophthalmology Manila Doctors HospitalManila 1000Philippines Department of ophthalmology Rizal Medical CenterPasig City 1600Philippines Department of ophthalmology Jose B.Lingad Memorial Regional HospitalPampanga 2000Philippines Department of ophthalmology Southern Philippines Medical CenterDavao City 8000Philippines Department of ophthalmology East Avenue Medical CenterQuezon City 1100Philippines Department of ophthalmology Northern Mindanao Medical CenterCagayan de Oro City 9000Philippines Department of ophthalmology Cebu Velez General HospitalCebu City 6000Philippines Legazpi Eye center Legazpi City 4500Philippines Department of ophthalmology Cagayan Valley Medical CenterTuguegarao City 3500Philippines

AIM:To provide a comprehensive and more representative national data on the disease,especially on treatment options and outcomes,and to determine access of retinoblastoma patients from Luzon,Visayas and Mindanao to eye care,and determine if access is associated with delay in consultation,staging and ***:Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon,Vizayas and Mindanao from ***:Totally 636 patients,involving 821 eyes,were ***(57%)were from Luzon and were seen in institutions in Luzon(72%).Annually,58±10 new cases were seen with 71%having unilateral *** delay of consultation remained long at 9(3,17)mo,longest in patients with unilateral disease(Pal Retinoblastoma Staging System,only 35%of patients had Stage 1 while 47%already had extraocular *** was the most common treatment received by 484 patients while intravenous chemotherapy was received by *** were 250(39%)patients alive,195(31%)dead,85(13%)abandoned,17(3%)refused and 89(14%)with no ***:This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’and participating institutions’number and geographical location and type of institution(private and public).It also presents more comprehensive data on the treatments used and outcomes(survival,globe salvage,and vision retention rates).Delay in consultation was still long among patients leading to advanced disease stage and lower survival *** increasing capacity to diagnose and manage retinoblastoma in the country,the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial *** delay was still significant that overall survival rate remain low.

关键词： retinoblastoma Philippines clinical profile

Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

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Neural Regeneration Research 2025年第4期20卷 1079-1080页

作者： Victor V.Chizhikov Igor Y.Iskusnykh Department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in *** cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

关键词： epithelium Figure center