年龄相关性黄斑变性及息肉状脉络膜血管病变患者房水中不同亚型VEGF含量的测定

Concentrations of different isoforms of VEGF in aqueous humor in patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

背景 息肉状脉络膜血管病变（PCV）是湿性年龄相关性黄斑变性（nAMD）的一个亚型还是独立于nAMD一种病变目前仍有不同的观点,而两种疾病的治疗效果可能不同.抗血管内皮生长因子（VEGF）在nAMD的治疗中发挥重要作用,但由VEGF可变剪切而产生的促新生血管生成VEGF（VEGFxxx）家族和抑新生血管VEGF（VEGFxxxb）家族,两者功能相反,其在nAMD和PCV中的表达及作用尚不清楚. 目的 检测和比较VEGFxxx家族和VEGFxxxb家族在nAMD患者和PCV患者房水中的变化及其意义. 方法 收集2013年3-12月在北京大学人民医院眼科确诊的nAMD患者34例及PCV患者26例,同期纳入16例年龄相关性白内障患者作为对照.收集被检者前房水0.1 ml,采用酶联免疫吸附试验（ELISA）测定前房水中VEGF及VEGF165b质量浓度,比较3组患者房水中VEGF及VEGF165b质量浓度的差异. 结果 nAMD组、PCV组、对照组患者房水中VEGF质量浓度分别为（4 210.00±998.40）、（387.00±51.31）和（377.40±69.97） pg/ml,组间总体差异有统计学意义（F=12.851,P=0.000）.nAMD组、PCV组、对照组VEGF165b质量浓度分别为（205.50±12.59）、（159.40± 16.25）、（347.90±29.18） pg/ml,组间总体比较差异有统计学意义（F=23.752,P=0.000）.与对照组比较,nAMD组患眼房水中VEGF质量浓度升高,VEGF165b质量浓度下降,PCV组患眼房水中VEGF165b表达下降,差异均有统计学意义（均P=0.000）,但PCV组与对照组患眼房水中VEGF含量差异无统计学意义（P=0.992）.nAMD组较PCV组房水中VEGF质量浓度升高,差异有统计学意义（P=0.001）,但两组间VEGF165b质量浓度差异无统计学意义（P=0.097）. 结论 nAMD患者前房水中的VEGF质量浓度明显高于PCV患者和年龄相关性白内障患者,nAMD患者与PCV患者房水中VEGF165b质量浓度接近,但均低于年龄相关性白内障患者,说明VEGF165b质量浓度的相对下降与nAMD和PCV的发生和发展密切相关.

Background There remains some controversy over whether polypoidal choroidal vasculopathy （PCV） represents a subtype of neovascular age-related macular degeneration （nAMD）.Anti-vascular endothelial growth factor （VEGF） therapies are important in the treatment of PCV and nAMD.It has been identified that VEGF-A was differentially spliced from exons 8 and formed two isoforms families：the pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family.However,the role of the two VEGF families in PCV and nAMD was still unclear.Objective This study was to measure the contents of pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family in aqueous humor of nAMD and PCV patients and explore their effect on nAMD and PCV.Methods Thirty-four nAMD patients and 26 PCV patients were enrolled in Peking University People＇s Hospital during March to December,2013,and 16 age-related cataract patients served as controls.The aqueous humor samples 0.1 ml was collected before the introvitreous injection of anti-VEGF drug.The contents of pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxx b family in the aqueous humor were measured by enzyme-linked immunosorbent assay（ELISA）.Results The concentrations of VEGF in the aqueous humor in the nAMD group,PCV group and control group were （4 210.00±998.40）,（387.00±51.31） and （377.40 ±69.97）pg/ml,respectively,showing a significant difference among the three groups （F =12.851,P =0.000）.The concentrations of VEGF165 b in the aqueous humor in the nAMD group,PCV group and control group were （205.50±12.59）,（159.40±16.25） and （347.90±29.18） pg/ml,with a significant difference among them （F=23.752,P=0.000）.Compared with the control group,VEGF content in the aqueous humor was elevated and the VEGF165b content was declined in the nAMD group,and VEGF165b was lowed in the PCV group,with significant differences between them（all at P=0.000）.However,no significant difference was seen in the change of VEGF between the PCV group and the control group （P=0.992）.The VEGF content in the aqueous humor was higher in the nAMD group than that in the PCV group （P =0.001）,but VEGF165b content was insignificantly different （P =0.097）.Conclusions The downregulation of VEGFxxx b may be associated with nAMD and PCV.The different role of VEGFxxx b in the development of PCV and nAMD needs to be verified in further studies.