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Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

International Journal of Ophthalmology(English edition) 2016年第1期9卷 41-47页

作者： Song Chen Wei Zhang Ji-Ming Wang Hong-Tao Duan Jia-Hui Kong Yue-Xin Wang Meng Dong Xue Bi Jian Song Tianjin eye Hospital Tianjin Key Lab of Ophthalmology and Visual Science Tianjin Eye Institute Clinical College of Ophthalmology Tianjin Medical University

AIM：To investigate whether umbilical cord human mesenchymal stem cell（UC-MSC）was able to differentiate into neural stem cell and neuron.·METHODS：The umbilical cords were o btained from pregnant women with their written consent and the approval of the Clinic Ethnics ***-MSC were isolated by adherent culture in the medium contains 20%fetal bovine serum（FBS）,then they were maintained in the medium contain 10%FBS and induced to neural cells in neural differentiation *** investigated whether UC-MSC was able to differentiate into neural stem cell and neuron by using flow cytometry,reverse transcriptase-polymerase chain reaction（RT-PCR）and immunofluorescence（IF）analyzes.·R ESULTS：A substantial number of UC-MSC was harvested using the tissue explants adherent method at about *** cytometric study revealed that these cells expressed common markers of MSCs,such as CD105（SH2）,CD73（SH3）and *** induction of differentiation of neural stem cells,the cells began to form clusters;RT-PCR and IF showed that the neuron specific enolase（NSE）and neurogenic differentiation 1-positive cells reached 87.3%±14.7%and 72.6%±11.8%,*** showed neuronal cell differentiation after induced,including neuron-like protrusions,plump cell body,obviously and stronger ***-PCR and IF analysis showed that microtubule-associated protein 2（MAP2）and nuclear factor-M-positive cells reached 43.1%±10.3%and 69.4%±19.5%,respectively.·CONCLUSION：Human umbilical cord derived MSCs can be cultured and proliferated and differentiate into neural stem cells,which may be a valuable source for cell therapy of neurodegenerative eye diseases.

关键词： human umbilical cord mesenchymal stemcells neural stem cells neuron neurodegenerative eye diseases

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Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo

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International Journal of Ophthalmology(English edition) 2018年第5期11卷 766-772页

作者： Jian Wang Wei Zhang Guang-Hui He Bin Wu Song Chen Tianjin eye Hospital Tianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteClinical College of Ophthalmology Tianjin Medical University

AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in ***：MSCs were infected by lentivirus constructed with *** expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain ***4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic ***4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of *** histological structure of DR in rats was inspected by hematoxylin and eosin *** expression of rhodopsin,neuron-specific enolase（NSE）,and inflammatory cytokines interleukin（IL）-6 and tumor necrosis factor（TNF）-α was examined by Western blot and immunohistochemical ***：The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and *** migration activities were observed in CXCR4-overexpressing ***,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in ***：The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of ***4-overexpressing MSCs can be a novel strategy for treating DR.

关键词： chemokine receptor type 4 diabetic retinopathy mesenchymal stem cells transplantation

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A growing field: the regulation of axonal regeneration by Wnt signaling

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Neural Regeneration Research 2018年第1期13卷 43-52页

作者： Armando L. Garcia Adanna Udeh Karthik Kalahasty Abigail S. Hackam Bascom Palmer eye institute University of Miami Miller School of Medicine Miami FL USA

The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system （CNS）. Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement.

关键词： Wnt signaling neuritogenesis retina retinal ganglion cell axonal growth regeneration spinal cord

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Response of L V Prasad eye institute to COVID-19 outbreak in India:experience at its tertiary eye care centre and adoption to its eye Health Pyramid

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International Journal of Ophthalmology(English edition) 2021年第1期14卷 1-9页

作者： Rohit C Khanna Prashant Garg Pravin K Vaddavalli Merle Fernandes Suryasnata Rath Sameera Nayak Raja Narayanan Rajeev Reddy Pappuru Swathi Kaliki Anthony Vipin Das Savitri Sharma Subhadra Jalali Allen Foster Community eye Health Research Centre Gullapalli Pratibha Rao International Centre for Advancement of Rural Eye CareL V Prasad Eye InstituteHyderabad 500030India Brien Holden eye Research Centre L V Prasad Eye InstituteHyderabadTelangana 500034India School of Optometry and Vision Science University of New South WalesSydney 2033Australia University of Rochester School of Medicine and DentistryRochesterNY 14642USA Kallam Anji Reddy Campus L V Prasad Eye InstituteHyderabad 500034India Grandhi Mallikarjun Rao Varalakshmi Campus L V Prasad Eye InstituteVishakhapatnamAndhra Pradesh 530040India Mithu Tulsi Chanrai Campus L V Prasad Eye InstituteBhubaneswaraOdisha 751024India Kode Venkatadri Chowdary Campus L V Prasad Eye InstituteVijayawada 521134India Department of eyeSmart EMR&Aeye L V Prasad Eye Institute 500034India

AIM:To summarize the experience of response to COVID-19 outbreak at a tertiary eye care institute and its network of health facilities in ***:Our responses are based on the principles of social distancing,hand hygiene,respiratory etiquettes,surface disinfection protocol,and rational use of appropriate personal protective equipment(PPE).We describe our response in terms of administrative controls,clinical protocols,staff protection,environmental controls,and social distancing *** also discuss our communication strategies and monitoring systems,to ensure compliance to ***:Administrative control is mainly related to formation of task force and its *** protocols are related to patient triaging methods and clinical examination guidelines in Outpatient,Inpatient and Operating *** protection is focused on training staff on the protocols to be followed in hospital as well as at home,and use of *** protocol is focused on cleaning and disinfectant methods to be used in the *** addition,there are systems for communication as well as monitoring compliance to ***:We hope that these protocols and our experience would help the ophthalmic community globally and serve as a guide to protect ophthalmologists and ophthalmic care personnel,and their patients across the world.

关键词： COVID-19 coronavirus India ophthalmology pandemic care practices pandemic protocols eye care

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Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae

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Neural Regeneration Research 2017年第12期12卷 2092-2099页

作者： Wen-wei Luo Zhao Han Dong-dong Ren Xin-wei Wang Fang-lu Chi Juan-mei Yang Department of Otolaryngology Eye & ENT Hospital of Fudan University Research institute of Otolaryngology Fudan University

Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.

关键词： nerve regeneration Atoh 1 DAPT. transdifferentiation gamma secretase inhibitor cochlea sensory epithelium fetal bovine serum hair cell supporting cell hair cell regeneration neural regeneration

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Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease

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Frontiers of Medicine 2023年第4期17卷 781-795页

作者： Yu Han Yu Zhang Kelan Yuan Yaying Wu Xiuming Jin Xiaodan Huang eye Center The Second Affiliated HospitalZhejiang University School of MedicineZhejiang Provincial Key Laboratory of OphthalmologyZhejiang Provincial Clinical Research Center for Eye DiseasesZhejiang Provincial Engineering Institute on Eye DiseasesHangzhou 310009China

Tear film hyperosmolarity plays a core role in the development of dry eye disease(DED)by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface *** this study,the mechanisms involving the hyperosmolar microenvironment,glycolysis mediating metabolic reprogramming,and pyroptosis were explored clinically,in vitro,and in *** from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes,including PKM2 and GSDMD,was significantly upregulated and that the secretion of IL-1βsignificantly *** vitro,the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells(HCECs)was used to discuss the interaction among *** hyperosmolar environment was found to greatly induce HCECs’metabolic reprogramming,which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression.2-Deoxy-d-glucose(2-DG)could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of *** vivo,2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and *** summary,our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

关键词： dry eye disease glycolytic reprogramming pyroptosis inflammation 2-DG

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PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland

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International Journal of Ophthalmology(English edition) 2020年第6期13卷 860-869页

作者： Peng-Yue Mu Chen-Chen Chu Di Yu Yan Shao Shao-Zhen Zhao Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science Eye Institute and School of OptometryTianjin Medical University Eye Hospital

AIM: To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor(PPAR)family in lacrimal gland dysfunction under conditions of desiccating stress or ***: Quantitative polymerase chain reaction(qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups:a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time(BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research,qP CR was used to examine the expression level of PPARγ,tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β),interleukin-6(IL-6), sirtuin 1(Sirt1), myeloid differentiation factor 88(MyD88) and transforming growth factor-β(TGF-β)in the lacrimal ***: PPARα and PPARβ/δ were mainly expressed in the conjunctiva and the lacrimal gland, ***, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARβ/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT,and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased(Peye diseases.

关键词： dry eye diabetes PPARγ rat lacrimal gland

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Ultrasonographic visualization of lower eyelid structures and dynamic motion analysis

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International Journal of Ophthalmology(English edition) 2013年第5期6卷 592-595页

作者： Mohammad Taher Rajabi Konstantinos Papageorgiou Shu-Hong Chang Imran Jarullazada Mehryar Taban Catherine J.Hwang Robert Alan Goldberg Division of Orbital and Ophthalmic Plastic Surgery Jules Stein Eye InstituteUniversity of California-Los Angeles eye Research Center Farabi Eye HospitalTehran University of Medical Sciences

AIMTo define the ultrasonographic structure of normal lower eyelid anatomic compartments and their spacial relationship in dynamic motion.

关键词： lower eyelid ultrasonography dynamic motion analysis

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Liquefaction for cataract extraction

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International Journal of Ophthalmology(English edition) 2016年第2期9卷 306-311页

作者： Georgios Labiris Aspasia Toli Damaskini Polychroni Maria Gkika Dimitrios Angelonias Vassilios P.Kozobolis Department of Ophthalmology University Hospital of Alexandroupolis eye institute of Thrace Democritus University

A systematic review of the recent literature regarding the implementation of the liquefaction in cataract surgery and its short-term and long-term outcomes in various parameters that affect the quality of patients＂ life, including visual rehabilitation and possible complications was performed based on the PubMed, Medline, Nature and the American Academy of Ophthalmology databases in November 2013 and data from 14 comparative studies were included in this narrative review. Liquefaction is an innovative technology for cataract extraction that uses micropulses of balanced salt solution to liquefy the lens nucleus. Most studies reported that liquefaction is a reliable technology for mild to moderate cataracts, while fragmentation difficulties may be encountered with harder nuclei.

关键词： Aqualase liquefaction cataract extraction endothelium corneal thermal injury

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Evaluation of a rat meibomian gland dysfunction model induced by closure of meibomian gland orifices

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International Journal of Ophthalmology(English edition) 2018年第7期11卷 1077-1083页

作者： Zi-Yi Dong Ming Ying Jie Zheng Lan-Jun Hu Jiang-Yan Xie Yi Ma Department of Ophthalmology Tianjin Union Medical Center Tianjin eye Hospital Tianjin Eye Institute Tianjin Key Lab of Ophthalmology and Visual Science

AIM： To find a stable, inexpensive, and reliable method to produce a rat meibomian gland dysfunction（MGD） model. METHODS： We inserted slim guidewires into the meibomian gland orifices of twelve Brown Norway rats and fulgurized every guidewire to destroy part of the meibomian gland. We then observed the morphological changes in the eyelid margin, and compared the data of tear breakup time（TBUT）, Schirmer I test, and the corneal fluorescence staining scores at different times（1, 2, 4, and 6 wk）. We observed pathological changes of the cornea, conjunctiva and meibomian gland, and we used real-time polymerase chain reaction to analyze epithelial growth factor（EGF）, interleukin-6（IL-6）, IL-8, tumor necrosis factor-α（TNF-α）, and Ki67. RESULTS： In the fourth week, compared with the control group, the TBUT of the model group began to decreased（P〈0.05）. The tear secretion remained stable（P〉0.05）. The corneal dots were significantly increased in the fourth week when the fusion stain began to appear（P〈0.05）. In the fourth week, partial meibomian gland openings had hoary secretions blocked, orifices were expanded, and there was a partial convex deformation. In the sixth week, the tissue section showed that the number of conjunctival goblet cells was decreased, epithelial cells were irregular, the epithelium was detached and rough, and meibomian glands were lost. The expressions of EGF, IL-6, IL-8, and TNF-α in corneal, conjunctival, and meibomian tissues were highly increased（P〈0.05）, but no statistical difference was found in the expression of Ki67 in corneal and conjunctival tissues（P〉0.05）. CONCLUSION： The MGD rat model, produced via electrocauterization of meibomian gland orifices, matched clinical manifestations and cytokine levels. Our research provides a new method of achieving an MGD animal model.

关键词： meibomian gland dysfunction animal model epithelial growth factor interleukin-6 interleukin-8 tumornecrosis factor-α Ki67

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