TY - JOUR
T1 - The role of thrombin in proliferative vitreoretinopathy
AU - Bastiaans, Jeroen
AU - van Meurs, Jan C
AU - Mulder, Verena C
AU - Nagtzaam, Nicole M A
AU - Smits-te Nijenhuis, Marja
AU - Dufour-van den Goorbergh, Diana C M
AU - van Hagen, P Martin
AU - Hooijkaas, Herbert
AU - Dik, Willem A
N1 - Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2014/7/11
Y1 - 2014/7/11
N2 - PURPOSE: To determine the role of thrombin in the development of proliferative vitreoretinopathy (PVR).METHODS: Vitreous was collected from patients undergoing a vitrectomy (macular holes and puckers, n = 11 [controls]; retinal detachment without PVR development following vitrectomy, n = 15 [RRD1]; retinal detachment with PVR development within 6 months after vitrectomy, n = 11 [RRD2]; and established PVR, n = 14 [PVR]). Thrombin activity in vitreous was determined using a thrombin-specific chromogenic substrate. ARPE-19 cells were stimulated with 8× diluted vitreous samples in the presence and absence of hirudin. The samples were analyzed at t = 0 and t = 24 hours for the presence of 27 cytokines/chemokines and growth factors using a multiplex approach. In comparable studies, ARPE-19 cells were stimulated for 2 hours, and mRNA expression levels for CCL2, CXCL8, GMCSF, IL6, and PDGFB were determined by real-time quantitative (RQ)-PCR.RESULTS: Thrombin activity was significantly (P < 0.05) higher in vitreous of the PVR group compared to the other groups. Proliferative vitreoretinopathy vitreous stimulated the production of chemokine (C-C motif) ligand (CCL)2, chemokine (C-X-C motif) ligand (CXCL)8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and platelet-derived growth factor (PDGF)-BB by ARPE-19 to significantly (P < 0.05) higher levels than vitreous from the RRD1 and RRD2 groups. These effects of PVR vitreous were significantly (P < 0.05) reduced by hirudin. These data were confirmed by mRNA studies.CONCLUSIONS: Thrombin activity is increased in vitreous of patients with established PVR and is involved in the activation of proinflammatory and profibrotic pathways in RPE cells. Inhibition of thrombin activity may therefore represent a potential treatment option for proliferative vitreoretinopathy.
AB - PURPOSE: To determine the role of thrombin in the development of proliferative vitreoretinopathy (PVR).METHODS: Vitreous was collected from patients undergoing a vitrectomy (macular holes and puckers, n = 11 [controls]; retinal detachment without PVR development following vitrectomy, n = 15 [RRD1]; retinal detachment with PVR development within 6 months after vitrectomy, n = 11 [RRD2]; and established PVR, n = 14 [PVR]). Thrombin activity in vitreous was determined using a thrombin-specific chromogenic substrate. ARPE-19 cells were stimulated with 8× diluted vitreous samples in the presence and absence of hirudin. The samples were analyzed at t = 0 and t = 24 hours for the presence of 27 cytokines/chemokines and growth factors using a multiplex approach. In comparable studies, ARPE-19 cells were stimulated for 2 hours, and mRNA expression levels for CCL2, CXCL8, GMCSF, IL6, and PDGFB were determined by real-time quantitative (RQ)-PCR.RESULTS: Thrombin activity was significantly (P < 0.05) higher in vitreous of the PVR group compared to the other groups. Proliferative vitreoretinopathy vitreous stimulated the production of chemokine (C-C motif) ligand (CCL)2, chemokine (C-X-C motif) ligand (CXCL)8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and platelet-derived growth factor (PDGF)-BB by ARPE-19 to significantly (P < 0.05) higher levels than vitreous from the RRD1 and RRD2 groups. These effects of PVR vitreous were significantly (P < 0.05) reduced by hirudin. These data were confirmed by mRNA studies.CONCLUSIONS: Thrombin activity is increased in vitreous of patients with established PVR and is involved in the activation of proinflammatory and profibrotic pathways in RPE cells. Inhibition of thrombin activity may therefore represent a potential treatment option for proliferative vitreoretinopathy.
KW - Aged
KW - Cell Line
KW - Cytokines/genetics
KW - Female
KW - Gene Expression Regulation/physiology
KW - Humans
KW - Male
KW - Middle Aged
KW - RNA, Messenger/genetics
KW - Real-Time Polymerase Chain Reaction
KW - Retinal Detachment/surgery
KW - Retinal Perforations/surgery
KW - Retinal Pigment Epithelium/metabolism
KW - Thrombin/physiology
KW - Vitrectomy
KW - Vitreoretinopathy, Proliferative/metabolism
KW - Vitreous Body/metabolism
U2 - 10.1167/iovs.14-14818
DO - 10.1167/iovs.14-14818
M3 - Article
C2 - 25015355
SN - 0146-0404
VL - 55
SP - 4659
EP - 4666
JO - Investigative ophthalmology & visual science
JF - Investigative ophthalmology & visual science
IS - 7
ER -