Molecular mechanisms of subretinal fibrosis in age-related macular degeneration. (January 2016)

• Record Type: Journal Article
• Authors: Ishikawa, Keijiro; Kannan, Ram; Hinton, David R.
• Is Part Of: Experimental eye research. Volume 142(2016:Jan.)
• Page Start: 19
• Page End: 25
• Publication Date: 2016-01
• Subjects: Extracellular matrix -- Epithelial–mesenchymal transition -- Growth factor -- Laser-induced choroidal neovascularization -- Macrophage -- Matricellular protein -- Myofibroblasts -- Subretinal scar; α-SMA alpha-smooth muscle actin -- BM bone marrow -- CNV choroidal neovascularization -- CNVMs choroidal neovascular membranes -- CTGF connective tissue growth factor -- ECM extracellular matrix -- EGF epidermal growth factor -- EMT epithelial–mesenchymal transition -- FAK focal adhesion kinase -- FGF fibroblast growth factor -- FN fibronectin -- MAPK mitogen-activated protein kinase -- MMPs matrix metalloproteinase -- nAMD neovascular age-related macular degeneration -- PDGF platelet derived growth factor -- PDR proliferative diabetic retinopathy -- PI3K phosphatidylinositol-3 kinase -- POSTN periostin -- PVR proliferative vitreoretinopathy -- RPE retinal pigment epithelium -- S1P sphingosine-1-phosphate -- SPARC osteonectin -- TGF-β transforming growth factor-β -- TNC tenascin -- TNF-α tumor necrosis factor-α -- TSP1 thrombospondin 1 -- VEGF vascular endothelial growth factor -- ZEB zinc finger E-box-binding homeobox -- ZO-1 zonula occludens protein-1; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2015.03.009
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Subretinal fibrosis is a result of a wound healing response that follows choroidal neovascularization in neovascular age-related macular degeneration (nAMD). Although anti-vascular endothelial growth factor therapy has become a standard treatment that improves visual acuity in many nAMD patients, unsuccessful treatment outcomes have often been attributed to the progression of subretinal fibrosis. In this review, we summarize the cellular and extracellular components of subretinal fibrous membranes and also discuss the possible molecular mechanisms including the functional involvement of growth factors and the inflammatory response in the process. Moreover, we present an murine animal model of subretinal fibrosis that might facilitate greater understanding of the pathophysiology and the development of novel therapeutic strategies for the inhibition of subretinal fibrosis in nAMD. Highlights: Clinical implications of subretinal fibrosis in AMD. Cellular and extracellular components of subretinal fibrous membranes. Growth factors and epithelial–mesenchymal transition in subretinal fibrosis. Immune response related to subretinal fibrosis. Use of the laser-induced murine model of CNV to study subretinal fibrosis.