杨培增
葡萄膜炎
个性化签名
- 姓名:杨培增
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者,
- 职称:-
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学科领域:
眼科学
- 研究兴趣:葡萄膜炎
1982年毕业于河南医学院医疗系,1987年在河南医科大学获硕士学位,1990年于中山医科大学获博士学位。1990年至今在中山眼科中心工作,1995年破格晋升为教授,1998年被聘为博士生导师。一直从事葡萄膜炎研究,多次与荷兰、美国著名眼科研究所合作。在我国率先诱导出实验性自身免疫性葡萄膜炎(EAU)模型;在国际上首次提出内毒素诱导的葡萄膜炎(EIU)可以作为人类全葡萄膜炎动模模型的观点;发现人视网膜中有两层网状分布的MHC-II类抗原阳性细胞;揭示出猪视网膜与人视网膜有相似的免疫活性细胞分布特征;揭示出浸润细胞凋亡是EIU和EAU迅速消退的重要机制;阐明了人葡萄膜炎慢性化和复发的机制;发现一些免疫抑制剂可逆转患者淋巴细胞对凋亡的抵抗性;揭示出T-bet激活在葡萄膜炎的发生中起着重要作用;探讨了我国葡萄膜炎发病和分布规律,制定出我国葡萄膜炎的分类体系和中西医结合治疗方案,为许多来自全国各地、部分来自美国、英国、法国、日本、澳大利亚、南韩、土耳其的顽固性葡萄膜炎患者挽救了视力,奠定了我国葡萄膜炎研究在国际中的地位。近年来在SCI杂志发表论文17篇,国内核心杂志发表论文70余篇,编写了《葡萄膜炎》和《临床葡萄膜炎》两本专著,共十余次在国际葡萄膜炎及相关会议上作特邀演讲或大会报告。应邀在北京、上海等20余个大中城市作专题演讲,推动了我国葡萄膜炎的研究,提高了葡萄膜炎的诊治水平,并提升了我国在国际葡萄膜炎研究领域中的地位。研究成果获国家科技进步三等奖(排名第一),获得了国家自然科学基金创新研究群体基金(学术带头人)、国家杰出青年基金、教育部跨世纪优秀人才培养计划基金等(均为项目负责人)600余万元。所领导的葡萄膜炎研究组获千百十工程先进团队奖。是国际葡萄膜炎研究组成员、国务院学位委员会第五届学科评议组成员、卫生部有突出贡献中青年专家、全国模范教师、《中华眼科杂志》等8份杂志编委。
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10
【期刊论文】Macrophages and MHC class II positive cells in the choroid during endotoxin induced uveitis
杨培增, P Yang, A F de Vos, A Kiilstra, Zhongshan, P Yang,
British Journal of Ophthalmology 1997; 81:396-401,-0001,():
-1年11月30日
Aimlbackground-Endotoxin induced uveitis has been regarded as a model for acute anterior uveitis and until now little was known about choroidal involvement. The aim of this study was to investigate changes in macrophages and MHC class II positive cells in the choroid of Lewis rats during endotoxin induced uveitis. Methods-Choroid-sclera wholemounts were isolated from normal Lewis rats and at different time points-4, 8, 16, 24, 48, 72, and 96 hours, and 7, 10, and 14 days after a footpad injection of 200 μg of lipopolysac-charide (LPS). Immunohistochemistry was performed using the monoclonal antibodies EDI (monocytes, macro phages, dendritic cells), and OX6 (MHC class II antigen).Results-In normal rats, two layers of macrophages were identified in the choroid; a layer located immediately beneath the retinal pigment epithelium (RPE) and a layer bordering the sclera.The density of EDI positive cells in the layer bordering the RPE cells was 902 (SD 132) cells/mm2 whereas the sclerai layer had a cell density of 389 (73) cellslmm:2.Based on morphology, positive cells could be divided into two main categories; pleomorphiclround cells and dendrite form cells with varying appearances, with the latter being predominant in normal eyes. A network of MHC class II positive dendritic cells was found in the choroid, beneath the RPE, with a density of 659 (96) cells/ram2. No MHC class II positive cells were found in the macrophage layer bordering the sclera. LPS injection caused a massive influx of ED1 positive macro phages in the area below the RPE cells but did not result in an influx of macrophages at the scleral side of the choroid. The infiltrate reached a maximum at 16 hours following LPS injection and decreased at 96 hours. The morphology of the infiltrating cells was pleomorphic/round at early stages of inflammation and changed into a dendritlform cell population later. The number of MHC class II positive cells on the anterior side of the choroid increased 8 hours after injection and reached a peak at 72-96 hours. MHC class II positive cellswere not observed in the vicinity of the sclera at any time after LPS injection. Both resident and MHC class II positive dendritic cell numbers returned to norreal values at day 14 following LPS injection. Conclusions-These results indicate that the choroid is severely inflamed after systemic LPS administration to Lewis rats and suggests that endotoxin induced uveitis may serve as a model for generalized uveitis in humans.
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杨培增, Peizeng Yang, *Alex F. de Vos, * and Aize Kijlstra*
Published by Lippincott-Raven Publishers Vol. 37, No.1, January 1996,-0001,():
-1年11月30日
Purpose. To investigate the density, distribution, and morphology of macrophages (bone marrow-derived microglia) and major histocompatibility complex (MHC) class II-positive cells in the retina of Lewis rats and the dynamics of these cells after systemic lipopolysaccharide (LPS) injection. Methods. Immunohistochemistry was carried out using monoclonal antibodies specific to monocytes and macrophages (ED1, ED2) and MHC class II-positive cells (OX-6) on whole-mounts of the retina obtained from Lewis rats before and at different time points after footpad injection of 200 g of LPS. Results. The inner layers of the normal retina contained a network of macrophages, whereby ED1 and ED2 staining revealed similar results. Macrophages were either dendritiform or pleiomorphic in morphology, with the former predominant. The density of positive cells was higher at the peripheral part and the periequatorial part (271
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【期刊论文】Distribution, markers, and functions of retinal microalia
杨培增, Ling Chen-, Peizeng Yang, Aize Kijlstra,
Ocular Immunology and Inflammation 2000, Vol. 10, No.1, pp. 27-39,-0001,():
-1年11月30日
Retinal microglia originate flom hemopoietic cells and invade the retina from the retinal margin and the optic disc, most likely via the blood vessels of the ciliary body and iris, and the retinal vasculature. respectively. The microglial precursors that appear in the retina 34-325oJerent microglia popula.prior to vascularization arc major histocompatibilily complex (MHC) class 1-and II-positive and express the CD45 marker, but lack specific macrophage markers. They differentiate into ramified parenchymal microglia in the adult retina. A second category of microglial precursors, which do express specific macrophage markers, migrate into the retina along with vascular precursors. They appear around blood vessels in the adult retina and are similar to macrophages or cells of the mononuclear phagocyte series (MPS). Microglia are distributed in the outer plexiform laver (OPL), outer nuclear laver (ONL), inner plexiform layer (IPL), ganglion cell layer (GCL), and nerve fiber laver (NFL) of the primate retina. The pattern of microglial distribution in the avascular retina of the quail indicates that blood vessels are not responsible for the final location of microglia in the retina. In the human retina, microglia express MHC class l, MHC class II, CD45. CD68, and $22 markers. In the rat and mouse retina. OX41, OX42, OX3, OX6. OX18, ED1, Mac-l, F4/80, 5D4 anti-keralan sulfate, and lectins are used to recognize microglia. Microglial cells play an important role in host defense against invading microorganisms, immunoregulation, and tissue repair. During neurodegeneration, activated microglial cells participate in the phagocytosis ol debris and facilitate regenerative processes. In autoimnmne disease, microglia have dual functions: initialing uveoretinitis, but also limifing subsequent inflame marion. Retinal microglia may he associated wiih vitreoretinopathy, diabetic retinopathy, glaucoma, and age-related macular degeneration. The goal of this article was to review the present knowledge about retinal microglia and the function of retinal microglia in pathological conditions.
Retina, microglia, neurodegeneration, inflammation, AIDS, age-related macular degeneration, glaucoma
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【期刊论文】Localization and characterization of immunocompetent cells in the human retina
杨培增, Peizeng Yang-, Pranab K. Das, Aize Kijlstra,
Ocular Immunology and Inflammation 2000, Vol. 8, No.3, pp. 149-157,-0001,():
-1年11月30日
Purpose: Recent studies have shown that experimental uveitis can be induced by the appropriate administration of various retinal antigens. Little is known about the in-situ interactions between immune cells in the retina as a prerequisite for understanding the mechanisms involving the presentation of antigens by local antigen-presenting cells (APC) to invading T cells. The study described here was therefore designed to investigate the presence of immunocompetent cells with a focus on the characterization of retinal APCs. Materials and methods: Retinal whole mounts, cytospins, and ocular sections were prepared from eyebank eyes obtained within 24 hours postmortem. Immunohistochemistry (single staining and double staining) was performed on the retinal wholemounts, cytospins, and the ocular sections using monoclonal antibodies specific for HLA-DR (MHC class II), CD45 (leukocytes), CD68 (macrophages), CD2z (B cells), CD3 (T cells), and CDLa (dendritic cells). Results: CD68 positive macrophages were observed in one layer of the retina, whereas HLA-DR~ and CD45+ cells were seen in two distinct planes: one mainly at the level of the inner nuclear layer to outer plexiform layer (deep layer) and the other mainly at the nerve fiber and ganglion cell layer (shallow layer). There was a significant difference between the different parts of the retina with regard to the density of these cells. Cell density decreased when going from the peripheral to the posterior areas of the retina. The positive cells in the deep layer were frequently associated with blood vessels, whereas the cells in the shallow layer were distributed evenly throughout the retina. Most positive cells displayed a dendritiform appearance, whereas few cells showed a pleiomorphic morphology. Very few CDIa-positive cells were noted in the retina. Neither T cells (CD3) nor B cells (CD22) could be detected in the normal human retina. Double staining showed that the majority (83.7%) of the CD45~ cell population Was I-ILA-DR-positive, whereas approximately half (56.8%) the CD68~Cell population was HLA-DR-positive. Conclusions: This study shows that the human retina contains a number of different microglia populations, some of which express HLA-DR and could thus be involved in antigen presentation. Marked differences in cell density can be observed within the retina, with the most abundant presence seen in the peripheral retina. The normal retina contains few professional antigen-presenting cells (CDI+).
Macrophages, dendritic cells, microglia, retina, HLADR
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杨培增, Peizeng Yang, Li Ji, Hongyan Zhou, Xiangkun Huang, Chufang Xie, Haoli Jin, Ling Chen, Aize Kijlstra,
Ocular Immunology and Inflammation 2001, Vol. 9, No.3, pp. 185-191,-0001,():
-1年11月30日
Aims: To evaluate the expression of Fas/FasL antigen on peripheral blood T lymphocytes in patients with Behcet's disease, VogtKoyanagi-Harada (VKH) syndrome, and idiopathic anterior uveitis. Methods: The expression of Fas and FasL on peripheral blood T lymphocytes was determined using flow cytometry in 26 patients with Behcet's disease (BD), 17 patients with VKH syndrome, 25 patients with idiopathic anterior uveitis, and 43 healthy individuals (controls). Results: A higher proportion of CD4+T cells expressing Fas was noted in patients with Behcet's disease (25.70
Fas/, FasL, Behcet', s disease, Vogt-Koyanagi-Harada syndrome, anterior uveitis
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杨培增, peizeng Yang, Ling Chen, Hongyan Zhou, Huahong Zhong, Hong Wang, Xiangkun Huang, Aize Kijlstra-
Ocular Immunology and Inflammation 2002, Vol. 10, No.1, pp. 47-52,-0001,():
-1年11月30日
ononuclear cells were isolated by centrifugation with Ficoll-Paque and cultured in RPMI 164o with or without phytohemagglutinin (PHA) for 9h at 37℃ in an atmosphere with 5% CO2. The obtained cells were incubated with anti-Fas antibody for 8h at 37℃ in an atmosphere with 5% CO2. The cells were stained with annexin V/propidium iodide and finally subjected to flow cytometry. Results: A significantly lower percentage of apoptotic lymphocytes after PHA stimulation was noted in Behcet's disease (19.7±4.1%) and VKH syn drome (2o.4±6.9%) than in controls (26.1±7.3%). The percentage of apoptotic lymphocytes without PHA stimulation also tended to be lower in the patients with BehCet's disease (12.6%) and with VKH syndrome (12.8%) than in controls (14.6%), although the difference was not significant. Conclusion: Lymphocytes in patients with either Behcet's disease or VKH syndrome are relatively resistant to apoptosis mediated by anti-Fas antibody. These apoptosis-resistant, or longlived, lymphocytes may be involved in the chronic and recurrent intraocular inflammation seen in these patients.
Apoptosis, Behget', s disease, Vogt-Koyanagi-Harada syndrome
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【期刊论文】Macrophages and MHC class II positive dendritiform cells in the iris and choroid of the pig
杨培增, Ling Chen, , Rob Zwart, Peizeng Yang and Aize Kijlstra
Current Eye Research 2003, Vol. 26, No.5, pp. 291-296,-0001,():
-1年11月30日
shares many similarities with the human eye and is considered as a suitable species to investigate the pathogenesis of human ocular disease. The aim of this study was to investigate the presence of immunocompetent cells in the uveal tract of the normal pig. Methods. Iris and choroid wholemounts and cryostat sections were obtained from normal pig eyes. Single and double immunohistochemistry was performed by using anti-porcine leukocyte (CD45), anti-porcine macrophage (CD163, CD14), anti-porcine MHC class II (MCA1335), anti-human MHC class II (MCA379G), anti-porcine B lymphocyte (IgM), anti-porcine T lymphocyte (CD6) and anti-porcine granulocyte (MCA1219) monoclonal antibodies. Results. A rich network of dendritiform CD163 positive tissue macrophages was observed in normal pig iris and choroid wholemounts (368+84/mm2, 402+97/mm2, respectively). Approximately 50% of the CD163 positive tissue macrophages in the iris coexpressed MHC class II. Double immunostaining revealed that a small population of the MHC class II positive cells, did not express macrophage markers, and probably represent classical DCs. B lymphocytes and granulocytes were not detected in iris and choroid whole mounts. An occasional T cell could be observed per high power field in iris wholemounts but not in the choroid. Conclusions. The present study reveals that the normal piguveal tract contains a rich network of tissue macrophages and MHC class II positive dendritiform cells. At least three populations could be distinguished: MHC class II positive and negative tissue macrophages and MHC class II+ dendritiform cells lacking tissue macrophage markers.
pig, iris, choroid, macrophage, dendritic cells, immunocytochemistry
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【期刊论文】T-bet expression is upregulated in active Behcet's disease
杨培增, Li, P Yang, H Zhou, Z Zhang, C Xie, X Lin, X Huang, A Kijlstra
Br J Ophthalmol 2003, 87:1264-1267,-0001,():
-1年11月30日
Aim: To investigate T-bet mRNA and protein expression on peripheral blood monanuclear cells (PBMC) in patients with Behcet's disease with active uveitis. Methods: Blood samples were taken from 24 patients with Behcet's disease who had active uveitis and 16 healthy individuals. PBMC were subjected to analysis of T-bet mRNA nd protein expression using semiquatitative reverse tran scriptase-polymerase chain reaction (RT-PCR) and western blot, respectively. The products from PCR were sequenced. In order to determine the influence of activation on T-bet expression, the phytohaemagglutinin (PHA) stimulated PBMC from each sample were also evaluated for expression of T-bet mRNA and protein. Results: A significantly increased T-bet mRNA accumulation was detected in the samples from patients with active Behcet's disease compared with that in controls. A 62 kDa band was detectable in patients with active Behcet's disease, but not in controls. No difference was found between patients with Behcet's disease who had active uveitis and normal controls concerning the expression of either T-bet mRNA or its protein after stimulation with PHA for 72 hours. Conclusion: Behcet's disease is associated with an upregulation of T-bet expression, which supports a role for the Thl subset of T cells in the pathogenesis of this disease.
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【期刊论文】Visualization of cell Death In Vivo during Murine Endotoxin-Induced Uveitis
杨培增, Peizeng Yang, , Juxtine R. Smith, K. Sampatb Dmodar, Stepben R. Planck, and James T. Rosebaum
Invesigative Ophthalmologs & Visnal Science, May 2003, Vol. 44, No.5,-0001,():
-1年11月30日
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【期刊论文】Immune Cells in the Porcine Retina: Distribution, Characterization and Morphological Features
杨培增, Peizeng Yang, , Ling Chen, Rob Zwart, and Aize Kijlstra
IOVS, May 2002, Vol 43. No.3,-0001,():
-1年11月30日
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