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Entrainment of Astrocytic and Neuronal Ca^(2+) Population Dynamics During Information Processing of Working Memory in Mice

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Neuroscience Bulletin 2022年第5期38卷 474-488页

作者： Zhu Lin Feng You Ting Li Yijia Feng Xinyue Zhao Jingjing Yang Zhimo Yao Ying Gao Jiang-Fan Chen The Molecular Neuropharmacology Laboratory and the eyeBrain Research Center State Key Laboratory of OphthalmologyOptometry and Visual ScienceSchool of Optometry and Ophthalmology and Eye HospitalWenzhou Medical UniversityWenzhou 325035China

Astrocytes are increasingly recognized to play an active role in learning and memory,but whether neural inputs can trigger event-specific astrocytic Ca^(2+)dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca^(2+)dynamics in animals performing tasks.Here,using fiber photometry,we showed that population astrocytic Ca^(2+)dynamics in the hippocampus were gated by sensory inputs(centered at the turning point of the T-maze)and modified by the reward delivery during the encoding and retrieval phases.Notably,there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca^(2+)dynamics with a 3-s phase difference.Furthermore,there was a robust synchronization of astrocytic Ca^(2+)at the population level among the hippocampus,medial prefrontal cortex,and striatum.The inter-locked,bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

关键词： Working memory Ca^(2+)dynamics Astrocyte Neuron Fiber photometry Hippocampus

Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement

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Bioactive Materials 2022年第9期7卷 469-481页

作者： Siqing Zhu Huiying Huang Dong Liu Shimin Wen Liangliang Shen Quankui Lin Department of Biomaterials School of Ophthalmology&OptometryEye HospitalWenzhou Medical UniversityWenzhou325027PR China

Posterior capsular opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and differentiation of residual lens epithelial cells(LECs)on the surface of the intraocular lens(IOL).Although drug-loaded IOLs have been successfully developed,the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability.In this investigation,an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome.The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin(Dox)through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction.In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome,compared with free Dox,thus resulting in superior anti-proliferation effect.In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility.We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.

关键词： Exosome Intraocular lens Surface modification Targeted therapy Posterior capsular opacification

Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells,Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice

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Neuroscience Bulletin 2023年第7期39卷 1131-1145页

作者： Xue Li Shimin Zou Xiaomeng Tu Shishuai Hao Tian Jiang Jie-Guang Chen School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical UniversityWenzhou 325027China State Key Laboratory of optometry Ophthalmology and Vision Scienceand Zhejiang Provincial Key Laboratory of Optometry and OphthalmologyWenzhou 325027China Research Center for Translational Medicine the Afliated Wenling Hospital of Wenzhou Medical UniversityWenling 317500China

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intellectual disability,and congenital abnormalities.The etiology of NDDs is unclear.Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells(RGCs),respectively,in the mouse neocortex during early gestation.Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone(VZ).Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ.The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs.The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions,the loss of which leads to periventricular heterotopias.We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.

关键词： Neurogenesis Radial migration Radial glial cell Ventricular zone N-cadherin

Reversible grafting of antibiotics onto contact lens mediated by labile chemical bonds for smart prevention and treatment of corneal bacterial infections

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Journal of Materials Science & Technology 2021年第2期61卷 169-175页

作者： Bailiang Wang Jiahong Zeng Yishun Guo Lin Liang Yingyingjin Siyuan Qian Renjie Miao Liang Hu Fan Lu school of ophthalmology&optometry Eye HospitalWenzhou Medical UniversityWenzhou325027China

eye trauma, decreased immunity, and contact lens wear often cause serious bacterial infections and irreversible corneal damage. To realize the responsive release of antibiotics such as gentamicin sulfate(GS), a novel antibacterial contact lens was constructed through self-assembly of antibiotics loaded ADAGS/PEI(polyethyleneimine) multilayer films on the surface. Both in vitro and in vivo antibacterial tests demonstrated high efficient and fast antibacterial property based on the smart responsive to bacterial infections and reversible drug loading and release.

关键词： Contact lens Corneal infections Dynamic chemical bonds Schiff base reaction Multilayer films

Autocatalytic strategy for tuning drug release from peptide-drug supramolecular hydrogel

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Chinese Chemical Letters 2023年第10期34卷 204-208页

作者： Yuqin Wu Tian Xia Xiaohui Ma Lei Lei Lulu Du Xiaoning Xu Xiangyi Liu Yueting Shi Xingyi Li Deqing Lin Institute of Biomedical Engineering School of Ophthalmology&Optometry and Eye HospitalWenzhou Medical UniversityWenzhou 325027China

Peptide-drug conjugates(PDCs) composed of peptide, spacer and drug have gained extensive attention in the field of drug delivery owing to its precise control over the drug payload and architecture. However,the achievement of controllable and rapid drug release at targeted site by PDCs is still a great challenge for pharmaceutist. Herein, we introduced the histidine residue into PDCs to generate a supramolecular hydrogel via a p H-trigger strategy, which exhibited an autocatalytic effect to precisely tune drug release from PDCs hydrogel. Using indomethacin(Idm) as model drug, various PDCs(Y(Idm)EEH, Y(Idm)EEK and Y(Idm)EER) were synthesized and their self-assembling properties were investigated in terms of critical aggregation concentration(CAC), transmission electron microscopy(TEM) and rheometer. Introduction of histidine residue into PDCs presented a robust catalytic activity on the ester hydrolysis of p-nitrophenyl acetate in aqueous solution, as well conferred the autocatalytic capacity to hydrolyze the PDCs into active parent drug(Idm). Overall, we reported an autocatalytic activity of histidine residue to precisely tune drug release from PDCs hydrogels.

关键词： Peptide-drug conjugates Supramolecular hydrogel Autocatalysis Hydrolysis Drug release

Air tamponade and without heavy liquid usage in pars plana vitrectomy for rhegmatogenous retinal detachment repair

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International Journal of ophthalmology(English edition) 2018年第11期11卷 1779-1783页

作者： Zhong Lin Qi-Hua Liang Ke Lin Zhi-Xiang Hu Tian-Yu Chen Rong-Han Wu Nived Moonasar The eye hospital School of Ophthalmology and Optometry Wenzhou Medical University Department of ophthalmology University of the West Indies

AIM： To report the results of rhegmatogenous retinal detachment（RRD） repair after pars plana vitrectomy（PPV） without operative use of heavy liquid, and utilizing air tamponade in selected cases.METHODS： RRD patients without severity of proliferative vitreoretinopathy C2 or more underwent PPV without operative use of heavy liquid, and utilizing air tamponade were consecutively enrolled. Alternative postoperative facedown position or lateral position was required for 3-5 d.RESULTS： Totally 36 eyes of 36 patients（24 males, 66.7%） aged 53.8±10.9 y underwent this modified surgery. The mean number of retinal break was 2.1±1.3. Most of the eyes（29, 80.6%） had retinal detachment involving more than one quadrant. Twenty-two（61.1%） eyes with cataract had combined phacoemulsification and intraocular lens implantation. The mean follow up time was 4.6±1.8 mo. Two eyes with retinal redetachment underwent a second retinal repair surgery with silicone oil tamponade, yielding the primary reattachment rate to 94.4%（34/36）. Six（16.7%） eyes had intraocular pressure higher than 25 mm Hg. The visual acuity（logMAR） improved from 0.98±0.74 preoperatively to 0.52±0.31 postoperatively（P〈0.001）. CONCLUSION： The success rate of this modified retinal repair surgery is comparable with traditional surgery. This technique can be considered for certain retinal detachment patients, since its apparent advantages included lower surgical complications, reduced surgery expenditure, shorter time for postoperative facedown position, and avoiding silicone oil removal surgery.

关键词： air heavy liquid rhegmatogenous retinal detachment pars plana vitrectomy

Preliminary study on visual recognition under low visibility conditions caused by artificial dynamic smog

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International Journal of ophthalmology(English edition) 2018年第11期11卷 1821-1828页

作者： Xu-Hong Zhang Zhe-Yi Chen Bin-Bin Su Karunanedi Soobraydoo Hao-Ran Wu Qin-Zhuan Ren Lu Sun Fan Lyu Jun Jiang Department of optometry Eye Hospital of Wenzhou Medical University Aier school of ophthalmology Central South University

AIM： To quantitatively evaluate the effect of a simulated smog environment on human visual function by psychophysical methods.METHODS： The smog environment was simulated in a 40×40×60 cm3 glass chamber filled with a PM2.5 aerosol, and 14 subjects with normal visual function were examined by psychophysical methods with the foggy smog box placed in front of their eyes. The transmission of light through the smog box, an indication of the percentage concentration of smog, was determined with a luminance meter. Visual function under different smog concentrations was evaluated by the E-visual acuity, crowded E-visual acuity and contrast sensitivity.RESULTS： E-visual acuity, crowded E-visual acuity and contrast sensitivity were all impaired with a decrease in the transmission rate（TR） according to power functions, with invariable exponents of-1.41,-1.62 and-0.7, respectively, and R2 values of 0.99 for E and crowded E-visual acuity, 0.96 for contrast sensitivity. Crowded E-visual acuity decreased faster than E-visual acuity. There was a good correlation between the TR, extinction coefficient and visibility under heavy-smog conditions.CONCLUSION： Increases in smog concentration have a strong effect on visual function.

关键词： visual recognition low visibility conditions artificial smog

Contrast visual acuity after multifocal intraocular lens implantation: aspheric versus spherical design

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International Journal of ophthalmology(English edition) 2014年第1期7卷 100-103页

作者： Jun-Hua Li Yi-Fan Feng Yun-E Zhao Yin-Ying Zhao Lei Lin school of ophthalmology and optometry the Eye Hospital of Wenzhou Medical University Zhejiang eye hospital Department of ophthalmology Zhongshan HospitalFudan University

AIM: To evaluate contrast visual acuity(CVA) after implantation of an aspheric apodized diffractive intraocular lens(IOL) or a spherical apodized diffractive IOL in cataract surgery. ·METHODS: This prospective randomized controlled study with a 12-month follow-up compared the results of cataract surgery with implantation of an aspheric AcrySof ReSTOR SN6AD3 IOL(30 eyes) and a spherical AcrySof ReSTOR SN60D3 IOL(30 eyes). CVA with best distance correction was measured at 4 contrast levels(100%,25%,10% and 5%) under 3 levels of chart luminance [250,85 and 25 candelas per square meter(cd/m2)] using a multi-functional visual acuity tester(MFVA-100). ·RESULTS: At 12 months after surgery,there were no statistically significant differences in 100% CVA and 25% CVA under 250cd/m2(P100% =0.875 and P25% =0.057) and 85cd/m2(P100% =0.198 and P25% =0.193) between the aspheric group and the spherical group. However,the 10% CVA and 5% CVA were significant better in aspheric group than spherical group under 250cd/m2(P10% =0.042 and P5% = 0.007) and 85cd/m2(P10% =0.002 and P5%=0.039). Under the luminance level of 25cd/m 2,no significant differences was found in the 100% CVA between the 2 group(P100% = 0.245),while aspheric group had better visual acuity in the remaining 3 contracts(P25% =0.023,P10% =0.026 and P5% = 0.002,respectively). ·CONCULSION: The aspheric AcrySof ReSTOR SN6AD3 IOL provided patients with better low-contrast visual acuity than the spherical AcrySof ReSTOR SN60D3 IOL.

关键词： cataract surgery intraocular lens contrast sensitivity visual acuity

Choroidal thickness and choriocapillaris vascular density in myopic anisometropia

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eye and Vision 2021年第1期8卷 467-476页

作者： Xinting Liu Zhiyi Lin Feifu Wang Xiaoyi Peng Wenwen He Dan Chen Meixiao Shen Fan Lu Jun Jiang school of ophthalmology and optometry Eye HospitalWenzhou Medical University270 Xueyuan RoadWenzhou 325027ZhejiangChina

Background:This study aims to examine interocular differences in the choroidal thickness and vascular density of the choriocapillaris in anisometropic myopes and to further explore the relationship between choroidal blood flow and myopia.Methods:The sample comprised 44 participants with anisometropic myopia,aged 9 to 18 years,with normal bestcorrected visual acuity.All participants underwent a series of examinations,including spherical equivalent refraction(SER)and axial length(AL),measured by a Lenstar optical biometer and optical coherence tomography angiography(OCTA)scanner.OCT measured the choroidal thickness,vascular density,and flow voids of the choriocapillaris,and a customized algorithm was implemented in MATLAB R2017a with the post-correction of AL.The choroidal thickness was measured at the fovea and 0.5,1.0,1.5,2.0,2.5,and 3.0 mm nasally,temporally,inferiorly,and superiorly to the fovea.The vascular density and the flow voids of the choriocapillaris were measured at a 0.6-mm-diameter central circle,and the 0.6-2.5 mm diameter circle in the nasal,temporal,inferior,and superior regions.Repeated-measured ANOVAs were used to analyze the interocular differences.Partial correlations with the K value and age adjustments were used to study the relationships between the choroidal thickness,the choriocapillaris vascular density and flow voids,the SER and AL.Results:The choroidal thickness of the more myopic eyes was significantly thinner than less myopic eyes(P≤0.001),and the flow voids in the more myopic eyes were more than less myopic eyes(P=0.002).There was no significant difference in the vascular density of the choriocapillaris between the more and less myopic eyes(P=0.525).However,when anisometropia was more than 1.50 D,the vascular density of choriocapillaris in the more myopic eyes was significantly less than the less myopic eyes(P=0.026).The interocular difference of the choroidal thickness was significantly correlated with the interocular difference in SER and AL in the center,superior,and inferior reg

关键词： Myopic anisometropia Choroidal choriocapillaris Choroidal thickness