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Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

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World Journal of Stem Cells 2024年第5期16卷 512-524页

作者： Hang Zhang Ling-Zi Wu Zhen-Yu Liu Zi-Bing Jin beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

关键词： Cell junction Cellular differentiation Extracellular vesicle Human induced pluripotent stem cells Transcriptomics Proteomics

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Treatment of lacrimal gland adenoid cystic carcinoma:a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 164-172页

作者： Hai-Han Yan Rui Liu Nan Wang Liang-Yuan Xu Qi-Han Guo Jing Li Jian-Min Ma beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Sciences Key LaboratoryBeijing 100730China

AIM:To evaluate lacrimal gland adenoid cystic carcinoma(LGACC)of prognosis in patients who underwent different treatment regimens.METHODS:We searched PubMed,EMBASE,and the Cochrane Library for studies done on the treatment of LGACC,between January 1987 and April 2022.A Metaanalysis was conducted to pool the 5-year overall survival rate(OR),and the 5-year recurrence rate(RR)and 5-year metastasis rate(MR)were assessed.RESULTS:The 30 studies involved 585 patients were included in the Meta-analysis.The pooled 5-year OR with surgery alone was 50%,the 5-year RR was 63%,and the 5-year MR was 34%.The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67%(95%CI 61%,73%),the 5-year RR was 41%,and the 5-year MR was 35%.The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72%(95%CI 59%,84%),the 5-year RR was 48%,and the 5-year MR was 36%.The pooled 5-year OR with surgery,intra-arterial cytoreductive chemotherapy,and adjuvant chemoradiotherapy combined was 78%(95%CI 68%,89%),the 5-year RR was 15%,and the 5-year MR was 27%.CONCLUSION:Comprehensive treatment is more effective than surgery alone.Surgery combined with intraarterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.

关键词： adenoid cystic carcinoma lacrimal gland Meta-analysis

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Magnetic resonance imaging of extraocular rectus muscles abnormalities in acute acquired concomitant esotropia

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 119-125页

作者： Jia-Yu Chen Li-Rong Zhang Jia-Wen Liu Jie Hao Hui-Xin Li Qiong-Yue Zhang Zhao-Hui Liu Jing Fu beijing tongren eye center Beijing Tongren HospitalBeijing Key Laboratory of Ophthalmology&Visual SciencesCapital Medical UniversityBeijing 100176China Department of Radiology Beijing Tongren HospitalCapital Medical UniversityBeijing 100176China Department of Industrial Engineering and Operation Research University of CaliforniaBerkeley 94720USA

AIM:To investigate the difference of medial rectus(MR)and lateral rectus(LR)between acute acquired concomitant esotropia(AACE)and the healthy controls(HCs)detected by magnetic resonance imaging(MRI).METHODS:A case-control study.Eighteen subjects with AACE and eighteen HCs were enrolled.MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner.Extraocular muscles(EOMs)were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator.To form posterior partial volumes(PPVs),the LR and MR cross-sections in the image planes 8,10,12,and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness.The data were classified according to the right eye,left eye,dominant eye,and non-dominant eye,and the differences in mean cross-sectional area,maximum cross-sectional area,and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively.RESULTS:There were no significant differences between the two groups of demographic characteristics.The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes(P=0.028).The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group(P=0.009,P=0.016).For the dominant eye,the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group(P=0.013),but not in the MR muscle(P=0.698).CONCLUSION:The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia.The LR muscle become larger to compensate for the enhanced convergence in the AACE.

关键词： acute acquired concomitant esotropia magnetic resonance imaging extraocular muscles

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Guiding function of positron emission tomographycomputed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 693-699页

作者： Xuan Zhang Qi-Han Guo Rui Liu Jing Li Ying-Chao Li Jian-Min Ma beijing Ophthalmology and Visual Sciences Key Laboratory Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100005China Tai’an City Central Hospital Qingdao UniversityTai’an 271000Shandong ProvinceChina

AIM:To explore the role of positron emission tomographycomputed tomography(PET-CT)examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma(OAML).METHODS:The general clinical data,postoperative PET-CT results,treatment regimens,and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected.Among the 21 patients,five patients underwent surgical treatment alone,13 patients underwent surgical treatment combined with radiotherapy,and three patients underwent surgical treatment combined with chemotherapy.RESULTS:The follow-up period ranged from 8 to 79mo,with four cases of recurrence and no deaths.Through PETCT examination,two patients exhibited both local ocular metabolic elevation and systemic metastasis,and one of these patients had cervical lymph node metastasis,while the other had submandibular and parotid gland metastasis.Nine patients showed only local ocular metabolic elevation,while 10 patients had no abnormal metabolic activity locally.CONCLUSION:PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection,aiding in precise disease staging,and facilitating the development of personalized treatment plans,ultimately improving patient prognosis.

关键词： ocular adnexal mucosa associated lymphoid tissue lymphoma positron emission tomographycomputed tomography ocular tumors

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Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 822-830页

作者： Fang Ruan Wen-Jun Kong Qian Fan Hong-Wei Dong Wei Zhang Wen-Bin Wei Ying Jie Department of Ophthalmology Beijing You’an HospitalCapital Medical UniversityBeijing Infectious Eye Disease Diagnosis and Treatment CenterBeijing 100069China beijing tongren eye center Beijing Tongren HospitalCapital Medical UniversityBeijing Institute of OphthalmologyBeijing Ophthalmology and Visual Sciences Key LabBeijing 100730China Tianjin eye Hospital Tianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteNankai University Affiliated Eye HospitalNankai University Eye InstituteNankai UniversityClinical College of OphthalmologyTianjin Medical UniversityTianjin 300020China

AIM:To evaluate dry eye disease(DED)symptomatology and mental health status in different COVID-19 patients.METHODS:A cross-sectional observational design was used.Totally 123 eligible adults(46.34%of men,age range,18-59y)with COVID-19 included in the study from August to November,2022.Ocular Surface Disease Index(OSDI),Five-item Dry eye Questionnaire(DEQ-5),Hospital Anxiety and Depression Scale(HADS),and Pittsburgh Sleep Quality Index(PSQI)were used in this study.RESULTS:OSDI scores were 6.82(1.25,15.91)in asymptomatic carriers,7.35(2.50,18.38)in mild cases,and 16.67(4.43,28.04)in recurrent cases,with 30.00%,35.56%,and 57.89%,respectively evaluated as having DED symptoms(χ2=7.049,P=0.029).DEQ-5 score varied from 2.00(0,6.00)in asymptomatic carriers,3.00(0,8.00)in mild cases,and 8.00(5.00,10.00)in recurrent cases,with 27.50%,33.33%,and 55.26%,respectively assessed as having DED symptoms(χ2=8.532,P=0.014).The prevalence of clinical anxiety(50.00%)and depression(47.37%)symptoms were also significantly higher in patients with recurrent infection(χ2=24.541,P<0.001;χ2=30.871,P<0.001).Recurrent infection was a risk factor for high OSDI scores[odds ratio,2.562;95%confidence interval(CI),1.631-7.979;P=0.033]and DEQ-5 scores(odds ratio,3.353;95%CI,1.038-8.834;P=0.043),whereas having a fixed occupation was a protective factor for OSDI scores(odds ratio,0.088;95%CI,0.022-0.360;P=0.001)and DEQ-5 scores(odds ratio,0.126;95%CI,0.039-0.405;P=0.001).CONCLUSION:Patients with recurrent COVID-19 have more severe symptoms of DED,anxiety,and depression.

关键词： COVID-19 dry eye disease recurrent infection mental health

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Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

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Neural Regeneration Research 2024年第5期19卷 1112-1118页

作者： Meng Wang Shi-Qi Yao Yao Huang Jia-Jian Liang Yanxuan Xu Shaowan Chen Yuhang Wang Tsz Kin Ng Wai Kit Chu Qi Cui Ling-Ping Cen Joint Shantou International eye center of Shantou University and The Chinese University of Hong Kong ShantouGuangdong ProvinceChina Shantou University Medical College ShantouGuangdong ProvinceChina beijing tongren eye center Beijing Tongren HospitalCapital Medical UniversityBeijingChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

关键词： casein kinase-2 glaucoma intraocular pressure elevation macrophages retinal ganglion cells

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Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population

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Biomedical and Environmental Sciences 2024年第2期37卷 196-203页

作者： WANG Dan Dan WANG An Xin ZHANG Xiao Li WEI Wen Bin WU Shou Ling ZHAO Xing Quan Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China China National Clinical Research center for Neurological Diseases Beijing 100070China beijing tongren eye center Beijing Key Laboratory of Ophthalmology and Visual ScienceBeijing Tongren HospitalCapital Medical UniversityBeijing 100005China Department of Cardiology Kailuan HospitalTangshan 063001HebeiChina

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

关键词： Retinal nerve fiber layer Cognitive impairment Polyvascular abnormality

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Ocular surface in patients with different degrees of myopia

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1313-1321页

作者： Yan-Yun Lyu Shuang Wang Xiao-Niao Chen Zhen-Yu Wang Shan-Shan Huang Yan Yuan Hong-Shuang Lu Wen-Li Yang Li-Ya Qiao Lei Tian Ying Jie tongren eye Care center Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical University and Beijing Ophthalmology and Visual Sciences Key LaboratoryBeijing 100730China Department of Ophthalmology the Third Medical Center of Chinese People’s Liberation Army General HospitalBeijing 100039China Department of Ophthalmology and Visual Science Tokyo Medical and Dental UniversityTokyo 113-8510Japan

AIM:To investigate the clinical features of the ocular surface in patients with different degrees of myopia.METHODS:A cross-sectional study was conducted involving 122 participants with myopia in beijing tongren Hospital from February to June,2023.After completing the Ocular Surface Disease Index(OSDI)score scale,measurements were taken for refraction,biometric parameters and ocular surface parameters.The prevalence,severity and related parameters of the dry eye among different groups based on axial length(AL)were compared.Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters.RESULTS:Statistically significant differences were observed in refractive error,corneal thickness,anterior chamber depth,and subfoveal choroidal thickness among the groups(all Peye increased significantly(Peye onset in myopic participants.The longer the AL,the more severe the dry eye is,with the increased CFS spots and tear film instability.Additionally,SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.

关键词： myopia axial length ocular surface dry eye

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Discovery of a normal-tension glaucoma-suspect rhesus macaque with craniocerebral injury:Hints of elevated translaminar cribrosa pressure difference

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Chinese Medical Journal 2024年第4期137卷 484-486页

作者： Jian Wu Qi Zhang Xu Jia Yingting Zhu Zhidong Li Shu Tu Ling Zhao Yifan Du Wei Liu Jiaoyan Ren Liangzhi Xu Hanxiang Yu Fagao Luo Wenru Su Ningli Wang Yehong Zhuo State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceSun Yat-sen UniversityGuangzhouGuangdong 510060China beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Sciences Key LaboratoryBeijing 100730China School of Food Sciences and Engineering South China University of TechnologyGuangzhouGuangdong 510641China Guangzhou Huazhen Biosciences GuangzhouGuangdong 510920China

To the Editor:Normal-tension glaucoma(NTG)is a progressive optic neuropathy characterized by irreversible blindness with statistically normal intraocular pressure(IOP)(≤21 mmHg),^([1,2])which makes early-stage diagnosis in the clinical practice difficult.Pathophysiological pathways underlying NTG include vascular dysregulation,toxic metabolite accumulation,and elevated translaminar cribrosa pressure difference(TLCPD).^([3])Although various small animal models have provided evidence of different pathophysiological mechanisms,the complicated clinical phenotype cannot be fully imitated by secondary disease models,and the gap between rodents and humans weakens their translational potential.Thus,the pathological changes associated with NTG remain unclear.

关键词： elevated glaucoma diagnosis

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Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2275-2284页

作者： Jinyuan Wang Jinlu Zhang Shicheng Yu Hongyan Li Shaohong Chen Jingting Luo Haibo Wang Yuxia Guan Haihan Zhang Shiyi Yin Huili Wang Heping Li Junle Liu Jingyuan Zhu Qiong Yang Ying Sha Chuan Zhang Yuhang Yang Xuan Yang Xifang Zhang Xiuli Zhao Likun Wang Liping Yang Wenbin Wei beijing tongren eye center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical University100730 BeijingChina School of Clinical Medicine Tsinghua University100084 BeijingChina Chigenovo Co. Ltd.102206 BeijingChina Department of Ophthalmology Peking University Third HospitalBeijing Key Laboratory of Restoration of Damaged Ocular NervePeking University Third Hospital100191 BeijingChina Department of Ophthalmology The Third People’s Hospital of Dalian116091 DalianChina Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).

关键词： cor dystrophy crystalline

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