title: Minireview: Fibronectin in retinal disease.
abstract: Retinal fibrosis, characterized by dysregulation of extracellular matrix (ECM) protein deposition by retinal endothelial cells, pigment epithelial cells, and other resident cell-types, is a unifying feature of several common retinal diseases. Fibronectin is an early constituent of newly deposited ECM and serves as a template for assembly of other ECM proteins, including collagens. Under physiologic conditions, fibronectin is found in all layers of Bruch's membrane. Proliferative vitreoretinopathy (PVR), a complication of retinal surgery, is characterized by ECM accumulation. Among the earliest histologic manifestations of diabetic retinopathy (DR) is capillary basement membrane thickening, which occurs due to perturbations in ECM homeostasis. Neovascularization, the hallmark of late stage DR as well as exudative age-related macular degeneration (AMD), involves ECM assembly as a scaffold for the aberrant new vessel architecture. Rodent models of retinal injury demonstrate a key role for fibronectin in complications characteristic of PVR, including retinal detachment. In mouse models of DR, reducing fibronectin gene expression has been shown to arrest the accumulation of ECM in the capillary basement membrane. Alterations in matrix metalloproteinase activity thought to be important in the pathogenesis of AMD impact the turnover of fibronectin matrix as well as collagens. Growth factors involved in PVR, AMD, and DR, such as PDGF and TGFβ, are known to stimulate fibronectin matrix assembly. A deeper understanding of how pathologic ECM deposition contributes to disease progression may help to identify novel targets for therapeutic intervention.
authors: Department of Ophthalmology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA charlesgmiller@gmail.com.
authors: Charles G
authors: CG
authors: Miller
authors: Department of Ophthalmology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.
authors: Greg
authors: G
authors: Budoff
authors: Department of Ophthalmology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.|NJ Retina, New Brunswick, NJ 08901-2066, USA.
authors: Jonathan L
authors: JL
authors: Prenner
authors: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
authors: Jean E
authors: JE
authors: Schwarzbauer
mesh_terms: D000818:Animals; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D057586:Vitreoretinal Surgery / Q000009:adverse effects*
chemical_list: D005353:Fibronectins
keywords: Fibronectin; age-related macular degeneration; diabetic retinopathy; extracellular matrix; fibrosis; neovascularization; proliferative vitreoretinopathy; retina