新生血管性青光眼患者房水中血小板源性生长因子-C和血管内皮生长因子水平的测定和分析

Detection and analysis of platelet-derived growth factor-c and vascular endothelial growth factor in ocular aqueous humor with neovascular glaucoma

背景新生血管性青光眼（NVG）是由不同病因引起的严重致盲眼病，与视网膜组织缺氧后分泌因子有关，如血管内皮生长因子（VEGF）等，但仅用抗VEGF疗法并不能完全抑制新生血管的生长。我们先前的研究发现，血小板源性生长因子-C（PDGF—C）参与眼内病理性新生血管的生成，但PDGF—C在NVG中的作用尚不清楚。目的定量检测NVG患者房水中VEGF和PDGF—C的质量浓度，为NVG的治疗提供新的思路。方法采用前瞻性队列研究方法，收集2014年1月至2015年8月在第四军医大学西京医院就诊的NVG患者62例62眼，其中10眼近1年内曾行视网膜光凝和／或冷凝治疗，其他52眼中原发病为视网膜中央静脉阻塞（CRVO）者16眼，糖尿病视网膜病变（DR）者20眼，视网膜脱离（RD）术后者5眼，视网膜血管炎（Eales病）者4眼，未知原因者7眼；虹膜新生血管Ⅱ级者13眼，Ⅲ级者29眼，Ⅳ级者10眼。同期纳入年龄相关性白内障患者11例11眼作为对照。分别于手术中采集受检眼房水0．1～0．2ml，应用ELISA法检测受检眼房水中VEGF和PDGF—C质量浓度。结果NVG组患眼房水中VEGF和PDGF—C质量浓度分别为（1138．17±69．31）ng／L和（29．80±1．64）ng／L，明显高于对照组的（679．54±49．81）ng／L和（18．60±1．85）ng／L，差异均有统计学意义（t=20．95、20．49，均P〈0．01）。视网膜光凝和／或冷凝组患眼房水中VEGF和PDGF—C质量浓度分别为（1095．99±52．71）ng／L和（28．55±0．94）ng／L，均低于非光凝和／或冷凝组的（1146．28±69．57）ng／L和（30．04±1．64）ng／L，差异均有统计学意义（t=-2．160，P=0．034；t=-2．760，P=0．008）。NVG患者房水中VEGF与PDGF-C质量浓度呈正相关（r=0．346，P=0．006）。不同原发病组间及不同虹膜新生血管分级组间患眼房水中VEGF和PDGF-C质量浓度的总体比较差异均无统计学意义（均P〉0．05）。结论NVG患者房水中VEGF和PDGF-C质量浓度明显升高，视网膜光凝和／或冷凝治疗可抑制VEGF和PDGF-C的产生，靶向抑制PDGF—C可为NVG的抗新生血管治疗提供新的选择。

Background Neovascular glaucoma （NVG） is a serious eye disease with a variety of causes. It results from the secretion of growth factors by hypoxie retinal tissue, such as vascular endothelial growth factor （ VEGF）, but anti-VEGF treatment alone dose not completely inhibit neovascularization. Our previous study found that platelet-derived growth factor-c （PDGF-C） is also an important factor in pathological angiogenesis. However,the role of PDGF-C in the development of NVG remains unknown. Objective This study was to quantitatively detect the levels of VEGF and PDGF-C in the aqueous humor of patients with NVG and provide a basis for the anti-angiogenesis therapy. Methods A prospective cohort study was carried out. Sixty-two eyes of 62 patients with advanced NVG and 11 control subjects with age related cataract were included in Xijing Hospital of the Fourth Military Medical University from January 2014 to August 2015. Ten of 62 NVG eyes received retinal photocoagulation and/or cryotherapy,and 16 eyes resulted from central retinal vein occlusion,20 eyes from diabetic retinopathy,5 eyes from postopeartion of retinal detachment,4 eyes from Eales disease and 7 eyes from unknown cause. Iris neovaseularization of grade Ⅱ was found in 13 eyes, grade m in 29 eyes and grade Ⅵ in 10 eyes. Aqueous humor specimen was collected for O. 1-0. 2 ml during the surgery, and the contents of VEGF and PDGF-C in the aqueous humor were detected by ELISA assay. Written informed consent was obtained from each subject prior to any medical procedure. Results The VEGF and PDGF-C concentrations in the aqueous humor were （ 1 138. 17±69.31 ） ng/L and （29.80± 1.64 ）ng/L in the NVG group, respectively ,which were significantly higher than （679.54±49.81）ng/L and （ 18.60± 1.85 ） ng/L in the control subjects （ t = 20.95,20.49, both at P〈0. 01 ）. The VEGF and PDGF-C concentrations in aqueous humor were （1 095.99±52.71 ）ng/L and （28.55±0.94）ng/L in the retinal photocoagulation group, showing significantly decreases in comparison with （ 1 146.28±69.57 ）ng/L and （30. 04±1.64）ng/L in the untreatment group （ t = -2. 160, P = 0. 034 ; t = - 2. 760, P = 0. 008 ）. The VEGF content in aqueous humor was positively correlated with PDGF-C content in the patients with NVG （r=0. 346 ,P=0. 006）. However,the aqueous levels of VEGF and PDGF-C were not significantly different among various primary disease groups and different iris neovascularitation gradings （all at P〉0.05）. Conclusions Both VEGF and PDGF-C contents in the aqueous humour are considerably elevated in NVG patients. Retinal photocoagulation and/or cryotherapy can inhibit the release of VEGF and PDGF-C in the aqueous humor. PDGF-C may be a target for the treatment of NVG.