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Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Müller cells

Chinese Medical Journal 2014年第19期127卷 3438-3442页

作者： Zhu Ruilin Cho Kin-Sang Chen Dong Feng Yang Liu Department of Ophthalmology Peking University First Hospital KeyLaboratory of Vision Loss and Restoration Ministry of EducationBeijing China schepens eye research institute Massachusetts Eye and EarHarvard Medical School Boston MA USA

Background In a previous study, we demonstrated that ephrin-A2 and -A3 negatively regulate the growth of neural progenitor cells in the central nervous system. Adult mice deficient in ephrin-A2 and -A3 （A2＋A3＋） displayed active ongoing neurogenesis throughout the brain, and mice deficient in ephrin-A3 alone showed increased proliferation of ciliary epithelium derived retinal stem cells. This study aimed to detect that the increase in proliferation and neurogenic potential of MOiler cells is influenced by the absence of ephrin-A2 and -A3. Methods We assessed the retinal and MOiler cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR. We cultured purified primary MOiler cells derived from wild-type and A2＋A3＋ mice in a defined culture medium that enables trans-differentiation of Mu11er cells into retinal neurons. To evaluate proliferating MOiler cells in vivo, we injected 5＇-ethylnyl-2-deoxiuridine （EdU） intraperitoneally to adult mice. Results Expression of ephrin-A2/A3 and their receptor EphA4 were detected in the retinas of adult mice, with EphA4 expression particularly enriched in MOiler cells. MOiler cells of A2＋A3＋ mice exhibited significantly elevated expression of retinal progenitor cell markers, Pax6 and Chx10, when compared with those from wild-type mice. Moreover, a higher percentage of Mu11er cells of A2＋A3＋ mice trans-differentiated and became recoverin＋ and β-Ⅲ-tublin＋ in the culture than those from wild type mice. Strikingly, an increased number of EdU＋ retinal cells was detected in the retinas of adult A2＋A3＋ mice as compared with wild-type mice. Conclusions Ephrin-A2 and -A3 are negative regulators of the proliferative and neurogenic potentials of Mu11er cells. Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage.

关键词： Muller cell stem cell retinal regeneration

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Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis

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International Journal of Ophthalmology(English edition) 2019年第1期12卷 123-128页

作者： Zhen-Zhen Guo Karen Chang Xin Wei Department of Ophthalmology West China Hospital Sichuan University Department of Ophthalmology First Hospital of Xi’an Graduate institute of Clinical Dentistry School of Dentistry Taiwan University schepens eye research institute MEEIHarvard Medical School

AIM: To systematically review whether the increased fluctuation of intraocular pressure(IOP) is a risk factor for open angle glaucoma(OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE,EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio(HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5 y. The combined HR was 1.23(95%CI 1.04-1.46, P=0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity(P<0.1).Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98(95%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43(95%CI1.13-1.82, P=0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10(95%CI 1.03-1.18, P=0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies(P=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presentedevidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.

关键词： intraocular pressure fluctuation glaucoma visual field progression

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Acute changes in ganglion cell layer thickness in ischemic optic neuropathy compared to optic neuritis using optical coherence tomography

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International Journal of Ophthalmology(English edition) 2020年第1期13卷 120-123页

作者： Peter W.MacIntosh S.Vijay Kumar V.R.Saravanan Virna M.Shah Illinois eye and ear Infirmary University of Illinois at ChicagoChicagoIL 60612USA Neuro-Ophthalmology Service Aravind Eye HospitalCoimbatore 641014India

AIM:To elucidate the changes of different ganglion cell layer(GCL)thinning patterns between the optic neuritis(ON)and non-arteritic anterior ischemic optic neuropathy(NAION).METHODS:A prospective,observational study was conducted to evaluate the timing of GCL changes between acute ON and NAION using optical coherence ***:Thinning on optical coherence tomography in the NAION group occurs as early as 11 d after symptomatic onset of vision loss and follows an altitudinal *** mean superior-inferior GCL thickness difference in the NAION cohort was clinically significant at 5.7μm in the NAION cohort compared to controls of 0.8μm(P=0.032),but not significant in the ON group compared to controls with both groups measuring 1.1μ*** thinning was significant for the ON group compared to controls at 7.2μm(P=0.011)but not the NAION group compared to controls at 1.35μ***:These findings suggest that future treatments for NAION should be given early,and possibly before 11 d in order to prevent GCL and irreversible vision loss.

关键词： optic neuritis non-arteritic ischemic optic neuropathy optical coherence tomography ganglion cell layer

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Evaluation of the new OxyPlate^(TM) Anaerobic System for the isolation of ocular anaerobic bacteria

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International Journal of Ophthalmology(English edition) 2012年第5期5卷 582-585页

作者： Emily K. Deschler Paul P. Thompson Regis Paul Kowalski Department of Ophthalmology University of Pittsburgh 203 Lothrop Street Ophthalmic Microbiology The Eye & Ear InstitutePittsburgh Pennsylvania 15213 United States

AIM: Anaerobic bacteria can cause ocular infections. We tested the OxyPlateTM Anaerobic System (OXY) to isolate pertinent anaerobic bacteria that can cause ocular ***: OXY, which does not require direct anaerobic conditions (i.e. bags, jars), was compared to conventional isolation of incubating culture media in anaerobic bags. Standard colonies counts were performed on anaerobic ocular bacterial isolates under aerobic and anaerobic conditions (anaerobic bags) using agar media: 1) OXY (aerobic only), 2) 5% sheep blood (SB), 3) Chocolate, and 4) Schaedler. The bacteria tested were de-identified ocular isolates cultured from endophthalmitis and dacryocystitis that include 10 Propionibacterium acnes and 3 Actinomyces species. The colony counts for each bacteria isolate, on each culturing condition, were ranked from largest to smallest, and non-parametrically compared to determine the best culturing ***: All anaerobic conditions were positive for all of the anaerobic isolates. SB and Schaedler’s agar under aerobic conditions did not support the growth of anaerobic bacteria. Sparse growth was noted on chocolate agar with Propionibacterium acnes . As an anaerobic system, SB in an anaerobic bag isolated higher colony counts than OXY (P=0.0028) and chocolate agar (P=0.0028).CONCLUSION: Although OXY did not test to be more efficient than other anaerobic systems, it appears to be a reasonable alternative for isolating anaerobic bacteria from ocular sites. The use of an agar medium in a specially designed plate, without the requirement of an anaerobic bag, rendered OXY as an advantage over other anaerobic systems.

关键词： anaerobic bacteria bacterial isolation endophthalmitis dacryocystitis

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Measurement of crystalline lens tilt in high myopic eyes before cataract surgery using swept-source optical coherence tomography

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eye and Vision 2020年第1期7卷 128-135页

作者： Qiang Lu Wenwen He Dongjin Qian Yi Lu Xiangjia Zhu Department of Ophthalmology Eye and EarNoseand Throat HospitalFudan University83 Fenyang RoadShanghai 200031People’s Republic of China eye institute Eye and EarNoseand Throat Hospital of Fudan UniversityShanghai 200031People’s Republic of China Key Laboratory of Myopia Ministry of HealthShanghai 200031People’s Republic of China Shanghai Key Laboratory of Visual Impairment and Restoration Shanghai 200031People’s Republic of China

Background:To measure the crystalline lens tilt in eyes with various degrees of myopia before cataract surgery using swept-source optical coherence tomography(SS-OCT).Methods:We used SS-OCT(IOLMaster 700)to scan 131 emmetropic eyes(axial lengtheyes(axial length 24.5–26 mm),and 123 high myopic eyes(52,29,and 42 eyes with axial lengths of 26–28,28–30,and>30 mm,respectively)as part of the routine preoperative examination before cataract ***-OCT involved B-scans along six *** data were analyzed to assess the magnitude and orientation of the lens tilt and their correlation with other optical biometric ***:The mean tilt was 3.36±0.98°in emmetropic eyes,3.07±1.04°in mild/medium myopic eyes,and 2.35±1.01°in high myopic *** correlated significantly and inversely with axial length(Pearson’s r=−0.427,Peyes,with mean angles of 24.32°and 147.36°in the right and left eyes,*** variability in the lens tilt direction increased with increasing axial length(χ^(2) test,P<0.001).Conclusion:The magnitude of crystalline lens tilt decreased with increasing axial *** direction of tilt was predominantly towards the upper outer quadrant in both *** variability in the tilt orientation increased with increasing axial *** registration:NIH(***),*** 23 February 2017.

关键词： Crystalline lens tilt Orientation Magnitude High myopia Swept-source optical coherence tomography

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Morphological features of anterior segment:factors influencing intraocular pressure after cataract surgery in nanophthalmos

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eye and Vision 2020年第2期7卷 454-464页

作者： Qiang Lu Wenwen He Yi Lu Xiangjia Zhu Department of Ophthalmology Eye and EarNoseand Throat HospitalFudan University83 Fenyang RoadShanghai 200031People’s Republic of China eye institute Eye and EarNoseand Throat Hospital of Fudan UniversityShanghai 200031People’s Republic of China Key Laboratory of Myopia Ministry of HealthShanghai 200031People’s Republic of China Shanghai Key Laboratory of Visual Impairment and Restoration Shanghai 200031People’s Republic of China

Purpose:To investigate the anterior segment in nanophthalmic eyes and their association with intraocular pressure after cataract ***:Thirty-two nanophthalmic eyes(axial length[AL]eyes(21≤AL≤24.5 mm)in 35 controls who had undergone uneventful cataract surgery were ***-source optical coherence tomography was used to compare the anterior segment structures between the two *** associations between the anterior segment characteristics of nanophthalmic eyes and postoperative intraocular pressure(IOP)were also ***:The IOP-lowering effect of cataract surgery was remarkably insufficient in nanophthalmic *** anterior synechiae(PAS)were observed in 56%(18/32)of nanophthalmic eyes,and a characteristic boomerangshaped iris was observed in 28%(9/32).The anterior surface of the iris seemed“smoother”in nanophthalmic eyes than in normal ***’s canal(SC)diameter,SC area,trabecular meshwork(TM)thickness,TM width,and TM area were generally smaller in the nanophthalmic *** age,higher preoperative IOP,broader PAS,and smaller SC area were main contributors to higher postoperative *** and SC diameter may also be of great importance in IOP prediction in patients without glaucoma surgery and ***:The morphological features of the anterior segment in nanophthalmic eyes are significantly different from those of normal *** factors such as age,AL,preoperative IOP,extent of PAS,SC and TM size could all be prognostic for IOP after cataract surgery in nanophthalmic eyes.

关键词： Nanophthalmos Anterior segment Intraocular pressure Catara

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Intrinsic determinants of optic nerve regeneration

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Chinese Medical Journal 2013年第13期126卷 2543-2547页

作者： ZHU Rui-lin CHO Kin-Sang GU0 Chen-ying CHEW Justin CHEN Dong-feng YANG Liu Department of Ophthalmology Peking University First Hospital Key Laboratory of Vision Loss and Restoration Ministry of Education Beijing 100034 China schepens eye research institute Massachusetts Eye and Ear Department of Ophthalmology Harvard Medical School Boston MA 02114 United States

Objective To review the functions of these intracellular signals in their regulation of retinal ganglion cell （RGC） axon regeneration. Data sources Relevant articles published in English or Chinese from 1970 to present were selected from PubMed. Searches were made using the terms ＂intrinsic determinants, axon regeneration, RGC, optic nerve regeneration, and central nervous system axon regeneration.＂ Study selection Articles studying the mechanisms controlling RGC and central nervous system （CNS） axon regeneration were reviewed. Articles focusing on the intrinsic determinants of axon regeneration were selected. Results Like other CNS neurons of mammals, RGCs undergo a developmental loss in their ability to grow axons as they mature, which is a critical contributing factor to the failure of nerve regeneration and repair after injury. This growth failure can be attributed, at least in part, by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation. Key intracellular signals and transcription factors, including B cell lymphoma/leukemia 2, cyclic adenine monophosphate, mammalian target of rapamycin, and Kr^Jppel-like transcription factors, have been identified to play central roles in this process. Conclusions Intense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration. More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.

关键词： nerve regeneration retinal ganglion cells, intrinsic determinants cAMP roTOR PTEN, SOCS3

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Developing leadership skills in young ophthalmologists

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Annals of eye Science 2019年第1期4卷 161-168页

作者： Catherine Green Alp Atik Margaret Hay Royal Victorian eye and ear Hospital MelbourneAustralia Monash institute for Health and Clinical Education Monash UniversityMelbourneAustralia

In a rapidly changing world,there is an increased need to cultivate ophthalmologists who are not only technically capable but also possess the leadership skills required to be at the forefront of *** make daily frontline decisions that determine the quality and efficiency of care based on their leadership ***,they also educate,advocate,perform research,run departments and work in practices-all of which require the practice of effective *** the need for ophthalmic leadership has been recognised,few training programs offer leadership skills as a component of their core curricula,focussing on clinical knowledge with less emphasis on teaching of non-clinical professional *** who participate in leadership development are more likely to feel empowered to provide patient-centred care,develop a greater self-awareness and confidence to initiate positive change and promote better team *** turn,the ophthalmic profession collectively benefits from effective leadership as organizations are better run,issues are advocated more globally and challenges are address holistically by ophthalmologists who are not merely technically capable surgeons or researchers,but effective communicators and *** this paper,we explore the role of leadership in the spheres of healthcare and *** discuss the value of leadership across clinical,educational and organisational levels,with specific emphasis on the current state of development and conclude with a series of recommendations to ensure the continued development of effective ophthalmic leaders into the future.

关键词： Ophthalmology leadership education

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Subretinal transplantation of mouse retinal progenitor cells

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Neural Regeneration research 2011年第7期6卷 500-504页

作者： Caihul Jiang Maonian Zhang Henry Klassen Michael Young Department of Ophthalmology Chinese PLA General Hospital Beijing 100853 China schepens eye research institute Department of Ophthalmology Harvard Medical School Boston 02114 MA USA Department of Ophthalmology School of Medicine University of California Irvine Orange 92868 CA USA

The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells （RPCs） were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.

关键词： retinal progenitor cell expansion retinal degenerative diseases subretinal transplantation retinal photocoagulation

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Inner blood-retina barrier involvement in dry age-related macular degeneration(AMD) pathology

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Neural Regeneration research 2020年第9期15卷 1656-1657页

作者： Natalie Hudson Mark Cahill Matthew Campbell Neurovascular Genetics Unit Smurfit Institute of GeneticsTrinity College DublinDublinIreland Royal Victoria eye and ear Hospital Adelaide RoadDublin 2Ireland

Age-relatedmaculardegeneration(AMD)isaprogressiveneurodegenerative disease with a global prevalence of 8.7%in people over the age of 45. It is one of the leading causes of central retinal blindness in the industrialized world leading to loss of an individual’s ability to read, drive and see fine details, such as recognition of faces. By 2040, it is estimated that 288 million individuals worldwide will be diagnosed with AMD due to improved life expectancy(Wong et al., 2014).

关键词： AMD individual degeneration

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