PDGF-α受体反义寡核苷酸治疗实验性增生性玻璃体视网膜病变  

Therapeutic effect of PDGF-α receptor ASODN on experimental proliferative vitreoretinopathy

作　　者：蒋姣姣[1] 彭燕一[2] 黄海[2] 李光辉[1] 

机构地区：[1]广西桂林医学院,广西壮族自治区桂林市541004 [2]广西桂林医学院附属医院眼科,广西壮族自治区桂林市541001

出　　处：《眼科新进展》2013年第9期812-815,821,共5页Recent Advances in Ophthalmology

基　　金：广西自然科学基金(编号:KY2012021);广西科学实验中心开放课题(编号:KFJJ2011-11)~~

摘　　要：目的探讨血小板源性生长因子α受体(platelet-derived growth factor receptorα,PDGFR-α)反义寡核苷酸治疗实验性增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)的效果。方法选择健康成年有色家兔24只(48眼),右眼分别行玻璃体内注射人视网膜色素上皮细胞(human retinal pigment epithelium,HRPE)稀释液(8只8眼,A组)、1.0与2.0μmol·L-1含PDGFR-α反义寡核苷酸及LipofectamineTM2000的HRPE细胞稀释液(各8只8眼,B组和C组)。左眼分别注射平衡盐溶液(balanced salt solution,BSS)0.1 mL作为正常对照组。造模后1周、2周、3周、4周间接眼底镜观察PVR程度;处死动物后,进行组织病理学观察眼底改变及免疫组织化学染色观察切片着色情况。结果造模前后正常对照组兔眼玻璃体透明,视网膜结构清楚;造模后28 d,A组兔眼玻璃体内可见粗大增生的条索及视网膜脱离,B组和C组严重度低于A组。在造模后1周、2周,PVR分级在所有组之间差异均无统计学意义(均为P>0.05);在3周、4周时,B组和C组的PVR分级明显低于A组(均为P<0.05)。造模后4周,B组TRD发生率(50%)和C组TRD发生率(38%)与A组(100%)相比,差异均有统计学意义(均为P<0.05);B组与C组相比,差异均无统计学意义(P>0.05)。组织病理学检查显示:造模后4周正常对照组全层结构清晰,A组兔视网膜内界膜粗糙、断裂或结构不清,各层结构欠清,神经节细胞水肿,出现空泡,数量减少,B组和C组严重度低于A组。免疫组织化学检查显示:A组视网膜全层细胞及增生的纤维组织内呈高强度棕黄色着色(++++),B组呈中等强度棕黄色着色(+++),C组呈较弱棕黄色着色(++);正常对照组视网膜表层神经节细胞、RPE内可见弱棕黄色着色(+)。结论 PDGFR-α反义寡核苷酸可降低PVR形成程度,这可能与下调视网膜细胞中PDGF-α浓度有关。Objective To explore the therapeutic effect of platelet-derived growth factor receptor a（PDGFR-a） antisense oligonucleotide（ASDON） on experimen- tal proliferative vitreoretinopathy （PVR）. Methods 24 healthy adult colored rabbits （48 eyes） were selected. Right eye intravitreous injections of human retinal pigment ep- ithelium（HRPE） diluents, HRPE diluents containing PDGFR-α ASDON and Lipofectami- neTM 2000（ 1.0μmol·L^-1 ） and HRPE diluents containing PDGFR-α ASDON and Lipo- fectamineTM 2000 （2.0μmol·L^-1） were randomly given to 8 rabbits （ 8 eyes）, respec- tively（ group A,B,and C）. All the 24 left eyes were given injections of 0.1 mL balanced salt solution（BSS） and recruited as the normal control group. PVR degree was observed at 4 points-in-time： 1 week,2 weeks,3 weeks and 4 weeks after modeling using indirect ophthalmoscope. Ocular fundus changes and slice staining were observed using his- topathological method and immunohistochemistry staining respectively after execution of all subjects. Results Vitreous bodies were transparent, and retinae were weli-or- ganized in eyes of the normal control group before and after modeling. At the 4th point- in-time,thick hyperplastic cord and retina detachment could be observed in group A, and conditions of group B and group C were less serious than that of group A. At the 1 st and 2nd point-in-time, no significant difference was observed among PVR degrees of the three groups（ All P 〉 0.05 ）. At the 3rd and 4th point-in-time, PVR degrees of group B and group C were significantly lower than that of group A （ Both P 〈 0.05 ）. TRD inci- dences in group B （50%） and group C （38%） were significantly lower than that in group A（ 100% ） at the 4th point-in-time （ Both P 〈 0.05 ） ; No statistical significance existed between TRD incidences in group B and group C （P 〉 0.05 ）. According to histopatho- logical exantination, at the 4th point-in-time full-thickness was well-organized in eyes of the normal co

关 键 词：增生性玻璃体视网膜病变 PDGF-α受体 反义寡核苷酸 兔 

分 类 号：R774.1[医药卫生—眼科]