The influence of systemic renin-angiotensin-inhibition on ocular cytokines related to proliferative vitreoretinopathy
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.
KeywordsProliferative vitreoretinopathy Treatment Angiotensin converting enzyme Renin Cytokines Growth factors
RH received support within the Köln Fortune study program from the University of Cologne. None of the authors has any conflicts of interest to declare regarding the content of this study.
Compliance with ethical standards
The University of Cologne provided financial support within the Köln Fortune study program in the form of funding personnel costs of RH and laboratory materials for the study. The sponsor had no role in the design or conduct of this research.
Conflict of interest
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 5.Gamulescu MA, Chen Y, He S, Spee C, Jin M, Ryan SJ, Hinton DR (2006) Transforming growth factor beta2-induced myofibroblastic differentiation of human retinal pigment epithelial cells: regulation by extracellular matrix proteins and hepatocyte growth factor. Exp Eye Res 83:212–222CrossRefPubMedGoogle Scholar
- 7.Kita T, Hata Y, Arita R, Kawahara S, Miura M, Nakao S, Mochizuki Y, Enaida H, Goto Y, Shimokawa H, Hafezi-Moghadam A, Ishibashi T (2008) Role of TGF-beta in proliferative vitreoretinal diseases and ROCK as a therapeutic target. Proc Natl Acad Sci U S A 105:17504–17509CrossRefPubMedPubMedCentralGoogle Scholar