The influence of systemic renin-angiotensin-inhibition on ocular cytokines related to proliferative vitreoretinopathy

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.