In patients with retinal detachment, the major cause of recurrent redetachment is proliferative vitreoretinopathy (PVR, 5-10 %). PVR is characterized by the formation of fibrotic contractile membranes on either side of the retina, causing the retina to detach. The retinal pigment epithelium (RPE) has an important role in the homeostasis and functioning of the retina and forms the outer blood-retinal barrier by separating the retina from the blood vessels in the choroid. Coagulation proteins may come in contact with the RPE due to hemorrhage or breakdown of the blood-retinal barrier. We were the first to demonstrate that vitreous of patients with established PVR contains elevated levels of thrombin. Intravitreal thrombin (and to some extent factor Xa) can induce the release of a broad panel of cytokines, chemokines and growth factors by RPE which regulate local inflammatory and fibrotic responses, fitting PVR pathogenesis. These responses include the differentiation of monocytes into macrophages and that of RPE into myofibroblasts. Both cell types are abundantly present in fibrotic retinal membranes. The clinically available direct thrombin-inhibitor Dabigatran is able to inhibit the thrombin-induced release of cytokines, chemokines and growth factors and may thus be an interesting therapy for PVR development and other vitreoretinal disorders which are characterized by breakdown of the blood-retinal barrier. Currently, in the Rotterdam Eye Hospital, it has been found that Dabigatran reaches the eye in a potential effective concentration and a clinical trial with Dabigatran is planned with patients at risk for developing PVR.

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J.C. van Meurs (Jan) , P.M. van Hagen (Martin)
Erasmus University Rotterdam
The studies were financially supported by Combined Ophthalmic Research Rotterdam (CORR-Project code: 3.1.0) and the International Retinal Research Foundation, Birmingham, Alabama, United States. The printing of this thesis was supported by the Erasmus University Medical Center, Ipsen Farmaceutica B.V., Landelijke Stichting voor Blinden en Slechtzienden, Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp and Stichting Ooglijders.
Erasmus MC: University Medical Center Rotterdam

Bastiaans, J. (2015, September 23). A novel role for coagulation proteins in the development of proliferative vitreoretinopathy. Retrieved from http://hdl.handle.net/1765/78638