Hoerster Robert, Fauser Sascha, Cursiefen Claus, Kirchhof Bernd, Heindl Ludwig M
Department of Ophthalmology, University of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.
Graefes Arch Clin Exp Ophthalmol. 2017 Sep;255(9):1721-1725. doi: 10.1007/s00417-017-3707-9. Epub 2017 Jun 9.
The renin-angiotensin system is involved in the pathogenesis of fibrosis in several organs via induction of transforming growth factor (TGF) beta. In the pathogenesis of proliferative vitreoretinopathy (PVR) TGF-beta plays a pivotal role, promoting transition of retinal pigment epithelial (RPE) cells into myofibroblasts. We studied the influence of angiotensin converting enzyme-inhibition (ACEI) on cytokines and growth factors, related to PVR in aqueous humor.
We performed a post hoc analysis of a prospectively conducted interventional case series. From patients with rhegmatogenous retinal detachment (RRD) aqueous humor was obtained during primary surgery and analyzed using multiplex bead analysis for interferon gamma, tumor necrosis factor alpha, CC-chemokine ligand (CCL) 2 / monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, platelet derived growth factor (PDGF)-aa, TGF-beta 1, TGF-beta 2, TGF-beta 3, fibroblast growth factor (FGF)-aa, and FGF-bb. We recorded information about systemic ACEI from the medical history.
In the primary study elevated levels of TGF-beta 1 and 2, IL 6 and 8 and CCL2/MCP-1 were a risk factor for later PVR development. Here, systemic ACEI neither influenced levels of these cytokines and growth factors, nor of any other tested in this study (p ≥ 0.438, respectively). Also the incidence of PVR development was unaffected (p = 0.201).
The systemic intake of ACEI for arterial hypertension does not influence levels of profibrotic cytokines/growth factors in aqueous humor. Further studies need to clarify if relevant levels of ACEI accumulate in the eye, and if direct administration of ACEI in experimental PVR could be beneficial.
肾素-血管紧张素系统通过诱导转化生长因子（TGF）β参与多个器官纤维化的发病机制。在增殖性玻璃体视网膜病变（PVR）的发病机制中，TGF-β起关键作用，促使视网膜色素上皮（RPE）细胞转变为肌成纤维细胞。我们研究了血管紧张素转换酶抑制（ACEI）对房水中与PVR相关的细胞因子和生长因子的影响。
我们对一项前瞻性进行的干预性病例系列进行了事后分析。从原发性手术期间的孔源性视网膜脱离（RRD）患者中获取房水，并使用多重微珠分析检测干扰素γ、肿瘤坏死因子α、CC趋化因子配体（CCL）2/单核细胞趋化蛋白（MCP）-1、白细胞介素（IL）-1β、IL-2、IL-4、IL-6、IL-8、血管内皮生长因子（VEGF）-A、血小板衍生生长因子（PDGF）-aa、TGF-β1、TGF-β2、TGF-β3、成纤维细胞生长因子（FGF）-aa和FGF-bb。我们从病史中记录有关全身性ACEI的信息。
在初步研究中，TGF-β1和2、IL-6和8以及CCL2/MCP-1水平升高是后期发生PVR的危险因素。在此，全身性ACEI既不影响这些细胞因子和生长因子的水平，也不影响本研究中检测的任何其他因子水平（p分别≥0.438）。PVR发生的发生率也未受影响（p = 0.201）。
用于治疗动脉高血压的全身性ACEI摄入不影响房水中促纤维化细胞因子/生长因子的水平。需要进一步研究以阐明ACEI的相关水平是否在眼中蓄积，以及在实验性PVR中直接给予ACEI是否有益。
