Mantel Irmela, Borgo Angelica, Guidotti Jacopo, Forestier Edwige, Kirsch Olga, Derradji Yasmine, Waridel Patrice, Burdet Frédéric, Mehl Florence, Schweizer Claude, Roduit Raphaël
Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Lausanne, Switzerland.
Protein Analysis Facility, University of Lausanne, Lausanne, Switzerland.
Front Pharmacol. 2020 Dec 29;11:594087. doi: 10.3389/fphar.2020.594087. eCollection 2020.
The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ = 0.001], interleukin-6 (IL-6) [ = 0.009], bioactive interleukin-12 (IL-12p40) [ = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ = 0.004], and hepatocyte growth factor (HGF) [ = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ < 0.0001] and IL-6 [ = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247.
新生血管性年龄相关性黄斑变性（nAMD）的标准治疗方法是玻璃体内注射抗血管内皮生长因子（VEGF）。然而，对于一些患者来说，即使进行最大剂量的抗VEGF治疗也不能完全抑制渗出活性。本研究的目的是在对抗VEGF治疗反应不完全的nAMD患者中识别分子生物标志物。收集了三组患者的房水（AH）样本：17例对抗VEGF反应不完全的nAMD患者（18只眼）、17例nAMD且治疗反应正常的患者（21只眼）以及16例无任何视网膜病变的对照患者（16只眼）。对这些样本进行了蛋白质组学和多重分析。蛋白质组学分析表明，对抗VEGF反应不完全的nAMD患者表现出炎症反应、补体激活、细胞溶解、蛋白质 - 脂质复合物和血管生成途径增加。多重分析显示，与正常反应者相比，反应不完全者中可溶性血管细胞黏附分子 - 1（sVCAM - 1）[P = 0.001]、白细胞介素 - 6（IL - 6）[P = 0.009]、生物活性白细胞介素 - 12（IL - 12p40）[P = 0.03]、纤溶酶原激活物抑制剂1型（PAI - 1）[P = 0.004]和肝细胞生长因子（HGF）[P = 0.004]水平显著升高。有趣的是，相同的生物标志物显示出高度的相互相关性，r2值在0.58至0.94之间。此外，我们通过AlphaLISA证实反应不完全组中sVCAM - 1[P < 0.0001]和IL - 6[P = 0.043]增加。nAMD中反应不完全者与激活的血管生成和炎症途径相关。尽管进行了最大剂量的抗VEGF治疗，nAMD的残余渗出活性可能与血管生成和炎症反应均有关，需要特定的辅助治疗。数据可通过ProteomeXchange获得，标识符为PXD02247。
