title: The role of CTGF in diabetic retinopathy.
abstract: Connective tissue growth factor (CTGF, CCN2) contributes to fibrotic responses in diabetic retinopathy, both before clinical manifestations occur in the pre-clinical stage of diabetic retinopathy (PCDR) and in proliferative diabetic retinopathy (PDR), the late clinical stage of the disease. CTGF is a secreted protein that modulates the actions of many growth factors and extracellular matrix (ECM) proteins, leading to tissue reorganization, such as ECM formation and remodeling, basal lamina (BL) thickening, pericyte apoptosis, angiogenesis, wound healing and fibrosis. In PCDR, CTGF contributes to thickening of the retinal capillary BL and is involved in loss of pericytes. In this stage, CTGF expression is induced by advanced glycation end products, and by growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β. In PDR, the switch from neovascularization to a fibrotic phase - the angio-fibrotic switch - in PDR is driven by CTGF, in a critical balance with vascular endothelial growth factor (VEGF). We discuss here the roles of CTGF in the pathogenesis of DR in relation to ECM remodeling and wound healing mechanisms, and explore whether CTGF may be a potential novel therapeutic target in the clinical management of early as well as late stages of DR.
authors.affiliation: Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: i.klaassen@amc.uva.nl.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Klaassen
authors.affiliation: Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: van Geest
authors.affiliation: Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Kuiper
authors.affiliation: Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cornelis J F
authors.initials: CJ
authors.lastname: van Noorden
authors.affiliation: Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Netherlands Institute for Neuroscience, Royal Academy of Sciences, Amsterdam, The Netherlands.
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
mesh_terms: D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000502:physiology*; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology
chemical_list: D055513:Connective Tissue Growth Factor
keywords: Angio-fibrotic switch; Basal lamina thickening; Connective tissue growth factor; Extracellular matrix; Pre-clinical diabetic retinopathy; Proliferative diabetic retinopathy; Wound healing