Karoline Baquet-Walscheid1,2, Lena Wildschütz3, Maren Kasper3, Martin Busch3, Solon Thanos4, Dirk Bauer3, Monika Stoll5,6, Simone König7, Arnd Heiligenhaus3,8. 1. Department of Ophthalmology and Ophtha-Lab, St. Franziskus-Hospital, Hohenzollernring 74, 48145, Münster, Germany. karoline.walscheid@uveitis-zentrum.de. 2. University of Duisburg-Essen, Essen, Germany. karoline.walscheid@uveitis-zentrum.de. 3. Department of Ophthalmology and Ophtha-Lab, St. Franziskus-Hospital, Hohenzollernring 74, 48145, Münster, Germany. 4. Institute of Experimental Ophthalmology, University of Muenster, Münster, Germany. 5. Core Facility Genomics, University of Muenster, Münster, Germany. 6. Department "Genetic Epidemiology", Institute of Human Genetics, University of Münster, Münster, Germany. 7. Core Unit Proteomics, Interdisciplinary Center for Clinical Research, University of Muenster, Münster, Germany. 8. University of Duisburg-Essen, Essen, Germany.
Abstract
PURPOSE: Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be observed clinically. METHODS: Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n = 30), acute anterior uveitis (AAU; n = 18), and primary open angle glaucoma (POAG; n = 20) were obtained during trabeculectomy or cataract surgery. Samples were analyzed by RNA-Seq, qRT-PCR, LC-IMS, Western-Blot, and LEGENDplex™ analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). RESULTS: RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG, p > 0.05). LC-IMS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which Angiopoetin, Lumican and Decorin were associated with angiogenesis and showed increased (p > 0.05) expression on Western-Blot analysis. LEGENDplex™ analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIA patients with treatment-refractory complicated course of uveitis. CONCLUSION: Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.
PURPOSE: Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be observed clinically. METHODS: Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n = 30), acute anterior uveitis (AAU; n = 18), and primary open angle glaucoma (POAG; n = 20) were obtained during trabeculectomy or cataract surgery. Samples were analyzed by RNA-Seq, qRT-PCR, LC-IMS, Western-Blot, and LEGENDplex™ analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). RESULTS: RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG, p > 0.05). LC-IMS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which Angiopoetin, Lumican and Decorin were associated with angiogenesis and showed increased (p > 0.05) expression on Western-Blot analysis. LEGENDplex™ analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIA patients with treatment-refractory complicated course of uveitis. CONCLUSION: Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.
Authors: A Heiligenhaus; H Michels; C Schumacher; I Kopp; U Neudorf; T Niehues; H Baus; M Becker; B Bertram; G Dannecker; C Deuter; I Foeldvari; M Frosch; G Ganser; M Gaubitz; G Gerdes; G Horneff; A Illhardt; F Mackensen; K Minden; U Pleyer; M Schneider; N Wagner; M Zierhut Journal: Rheumatol Int Date: 2011-11-15 Impact factor: 2.631
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Authors: A Heiligenhaus; K Minden; C Tappeiner; H Baus; B Bertram; C Deuter; I Foeldvari; D Föll; M Frosch; G Ganser; M Gaubitz; A Günther; C Heinz; G Horneff; C Huemer; I Kopp; C Lommatzsch; T Lutz; H Michels; T Neß; U Neudorf; U Pleyer; M Schneider; H Schulze-Koops; S Thurau; M Zierhut; H W Lehmann Journal: Semin Arthritis Rheum Date: 2018-12-04 Impact factor: 5.532
Authors: Anne-Mieke J W Haasnoot; Lenneke A Vernie; Aniki Rothova; Patricia V D Doe; Leonoor I Los; Nicoline E Schalij-Delfos; Joke H de Boer Journal: PLoS One Date: 2016-10-10 Impact factor: 3.240