Activation of C-Reactive Protein Proinflammatory Phenotype in the blood retinal barrier in vitro: Implications for Age-related Macular Degeneration

Sara Romero-Vázquez, Alfredo Adán, Marc Figueras-Roca, Victor Llorenç, Mark Slevin, Gemma Vilahur, Lina Badimon, Andrew D Dick, Blanca Molins

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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 leads 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.
Original languageEnglish
Pages (from-to)13905—13923
Number of pages19
JournalAging
Volume12
Issue number14
DOIs
Publication statusPublished - 16 Jul 2020

Keywords

  • age-related macular degeneration
  • retinal pigment epithelium
  • inflammation
  • C-reactive protein

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