Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro : Implications for age-related macular degeneration
Romero-Vázquez, Sara (Hospital Clínic i Provincial de Barcelona)
Adan Civera, Alfredo (Hospital Clínic i Provincial de Barcelona)
Figueras-Roca, Marc (Hospital Clínic i Provincial de Barcelona)
Llorenç, Victor (Hospital Clínic i Provincial de Barcelona)
Slevin, M. (Manchester Metropolitan University)
Vilahur, Gemma (Institut d'Investigació Biomèdica Sant Pau)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Dick, Andrew D (University College London Institute of Ophthalmology)
Molins, Blanca (Hospital Clínic i Provincial de Barcelona)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	The retinal pigment epithelium (RPE) is considered one of the main targets of age-related macular degeneration (AMD), the leading cause of irreversible vision loss among the ageing population worldwide. Persistent low grade inflammation and oxidative stress eventually lead to RPE dysfunction and disruption of the outer blood-retinal barrier (oBRB). Increased levels of circulating pentameric C-reactive protein (pCRP) are associated with higher risk of AMD. The monomeric form (mCRP) has been detected in drusen, the hallmark deposits associated with AMD, and we have found that mCRP induces oBRB disruption. However, it is unknown how mCRP is generated in the subretinal space. Using a Transwell model we found that both pCRP and mCRP can cross choroidal endothelial cells and reach the RPE in vitro and that mCRP, but not pCRP, is able to cross the RPE monolayer in ARPE-19 cells. Alternatively, mCRP can originate from the dissociation of pCRP in the surface of lipopolysaccharide-damaged RPE in both ARPE-19 and primary porcine RPE lines. In addition, we found that the proinflammatory phenotype of mCRP in the RPE depends on its topological localization. Together, our findings further support mCRP contribution to AMD progression enhancing oBRB disruption.
Grants:	Instituto de Salud Carlos III PI19/00265 Agencia Estatal de Investigación PGC2018-094025-B-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Age-related macular degeneration ; Retinal pigment epithelium ; Inflammation ; C-reactive protein
Published in:	Aging (Albany NY), Vol. 12 Núm. 14 (31 2020) , p. 13905-13923, ISSN 1945-4589

DOI: 10.18632/aging.103655
PMID: 32673285

19 p, 1.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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