论文标题:PDGF和VEGF抗体及AG1295抑制增生性玻璃体视网膜病变的实验研究
Research of PDGF Antibody VEGF Antibody AG1295 Inhibiting Proliferative Vitreoretinopathy
论文作者 葛丽娜
论文导师 吴雅臻,论文学位 硕士,论文专业 临床医学
论文单位 吉林大学,点击次数 157,论文页数 53页File Size3218k
2005-05-10论文网 http://www.lw23.com/lunwen_79597647/ 增生性玻璃体视网膜病变; 视网膜色素上皮细胞;PDGF VEGF ; AG1295 ; 动物模型
diabetic retinopathy; optic neuropathy; fundus fluorescein angiography
目的:评价血小板源性生长因子(PDGF)抗体、血管内皮生长因子(VEGF)抗体、血小板源性生长因子(PDGF)受体酪氨酸激酶抑制剂AG1295 对实验性增生性玻璃体视网膜病变(PVR)的防治作用。方法:将实验动物(兔)随机分组,制作成PVR 模型,将一定浓度的PDGF 抗体、VEGF 抗体、AG1295,BSS 液分别在当时及7 天时注入兔眼的玻璃体腔,每日观察兔眼情况,照眼底像,在28 天时处死兔子,取眼球,做病理切片及免疫组织化学染色。结果:观察实验动物:用间接检眼镜观察动物眼底,可见玻璃体有不规则灰白色细胞团,细胞团位于视盘前及髓线周围,增殖,产生细胞条索。随着增殖条索的增长,视网膜受到牵拉,可见髓线抬高、扭曲,血管也出现扭曲。进一步可见视网膜被拉起,产生局限性的视网膜脱离和全部视网膜脱离。局限性视网膜脱离产生的最早时间为第7 天;第28 天,对照组所有眼出现了不同程度的视网膜脱离,PVRⅤ级的占33%,实验组亦发生视网膜脱离,PVR 分级上以Ⅲ级为多,占38%。按Fastenberg 标准进行PVR 评分,玻璃体腔内注入200μg/mlPDGF 抗体0.1ml、200μg/mlVEGF 抗体0.1ml、AG1295 0.1ml 后第7 天、14 天时与单纯注入BSS 组比较,无显著性差异(P>0.05),在第21 天、28 天实验组与对照组有显著性差异(P<0.05),同是玻璃体腔内注入PDGF 抗体组,在制作动物模型时直接注入和第7 天时注入无显著性差异(P>0.05),在眼内注入VEGF 抗体、AG1295 组,结果无显著性差异(P>0.05)。病理检查:处死动物,将兔眼球大体沿子午线切开,肉眼所见与间接检眼镜所见相符。免疫组织化学染色:特定标记RPE 细胞及神经胶质细胞,计算免疫组织化学染色阳性细胞百分率,亦得出上面提到之结果。结论:在实
Proliferative vitreoretinopathy(PVR) is a disease process that occurs ineyes with rhegmatogenous retinal detachments and the complication of retinaldetachment surgery. Owing to trauma ,there will be proliferation of fibroustissue--traumatic PVR.PVR accounts for the majority of failures followingretinal detachment surgery. Retinal pigment epithelial (RPE) cells play apivotal role in the pathogenesis of proliferative vitreoretinopathy (PVR).TheStimulaition of inflammatory factors,RPE cells free、migrate、proliferate fromthe slit pore of retina, form proliferatove membrane in vitreous、superretinaand subretina、contracte, result in PVR.There are some factors in thepathogenesis of PVR,ep: platelet derived growth factor(PDGF)、vascularrendothelial growth factor(VEGF)、hepatocyte growth factor(HGF)、matrixmetallo proteinases(MMP)、tumor necrosis factor(TNF)、pigment epitheliumderived factor(PEDF)、fibroblast growth factor(FGF)、transforming growthfactor(TGF)、interleukin-1 interleukin interleukin and so on.The inhibition ofPVR is still the popular subject of ophthalmology.Now there are theremethods:drug,operation,gene therapy. Cutting proliferative tissue is maijormethod to inhibit PVR.Although vitrectomy has developed perfectly now,theeffectis not satisfactory.In this case,drugs inhibition of PVR has beenemphasized.At present, vitrectomyis still main method to inhibiting PVR,butthere are some recurrences of proliferative menmbrane in cases which haveserious proliferative vitreoretinopathy.Retinal detachment recur,patient isoperated secondary. Because of the radical operation、stimulation of siliconeoil 、postoperative inflammation, proliferative menmbrane recur. In theprevention of PVR,drugs are applicated when perfusing in PPV. The article plays special emphases upon PDGF and VEGF.PDGF isimportant in the chemotaxis and proliferation of RPE and glial cells, result inepiretinal membranes and subretinal membranes.The PDGF concentration invitreous of the patient associated with PVR is higher than that not associatedwith PVR,therefore it is applicable to injecting PDGF antibody tovitreous.VEGF is a multifunctional factor which accelerate neovascularizationand migrate、cleavage、proliferate RPE cells. Ozaki has maken advancement tocure neovascularization with inhibiting VEGF and its receptor.Some data showthat cell density of on vascular retinal proliferative membranes caused by PVRas lower than cell density in vascular retinal proliferative membranes causedby PDR .This implies that the treatment of PVR can not simply depent onthe inhibition of cell proliferation.So the prevent to neovascularizationis alsoimportant. The adult pigmented rabbits are experimentalanimal that they are injuredto form PVR. Adult pigmented rabbits were given 0.1 mL intravitrealinjections of 200μg/ml PDGF antibody 、200μg/ml VEGF antibody 、Platelet-derived growth factor receptor kinase inhibitor AG1295 at the firstday and the seventh day. Noninjected eyes served as controls.To observe fudusof eyes everyday,taking photos of fudus.On eh basis of Fastenbergstandard,PVR grades are classified. In eyes that received 200μg/ml PDGFantibody、200μg/ml VEGF antibody、Platelet-derived growth factor receptorkinase inhibitor AG1295, the photos of fudus show that sevsrity of PVR arelighter than in controls at the twenty-first and the twenty-eighth day
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