title: C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function.
abstract: The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic de Barcelona, Barcelona, Spain; bmolins@clinic.ub.es.|Institut Clínic d'Oftalmologia, Hospital Clínic de Barcelona, Barcelona, Spain; and.
authors.forename: Blanca
authors.identifier: http://orcid.org/0000-0003-0941-9134
authors.initials: B
authors.lastname: Molins
authors.forename: Anna
authors.initials: A
authors.lastname: Pascual
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic de Barcelona, Barcelona, Spain.|Department of Chemical Engineering and Material Sciences, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain.
authors.lastname: Méndez
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic de Barcelona, Barcelona, Spain.|Institut Clínic d'Oftalmologia, Hospital Clínic de Barcelona, Barcelona, Spain; and.
authors.forename: Victor
authors.initials: V
authors.lastname: Llorenç
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic de Barcelona, Barcelona, Spain.|Institut Clínic d'Oftalmologia, Hospital Clínic de Barcelona, Barcelona, Spain; and.
authors.forename: Javier
authors.initials: J
authors.lastname: Zarranz-Ventura
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic de Barcelona, Barcelona, Spain.|Institut Clínic d'Oftalmologia, Hospital Clínic de Barcelona, Barcelona, Spain; and.
authors.forename: Marina
authors.initials: M
authors.lastname: Mesquida
authors.affiliation: Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic de Barcelona, Barcelona, Spain.|Institut Clínic d'Oftalmologia, Hospital Clínic de Barcelona, Barcelona, Spain; and.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Adán
authors.affiliation: Department of Chemical Engineering and Material Sciences, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Martorell
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D001813:Blood-Retinal Barrier / Q000187:drug effects / Q000502:physiology*; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020033:Protein Isoforms / Q000737:chemistry / Q000528:radiation effects; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; D020033:Protein Isoforms; D002097:C-Reactive Protein
keywords: C-reactive protein; blood-retinal barrier; macular degeneration; tight junctions