Evidence map›Paper›PMID 40858941›Full record

ArticleScientific reports2025

C-reactive protein dissociation drives choroidal neovascularization in age-related macular degeneration.

Maria Hernandez, Sara Romero-Vázquez, Sergio Recalde, Jaione Bezunartea, Maite Moreno Orduña, Idoia Belza-Zuazu, Alfredo García-Layana, Alfredo Adán, Patricia Fernández-Robredo, Blanca Molins

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Macular degeneration collection.Scientific reports · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Maria HernandezRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain. mahersan@unav.es.
Sara Romero-VázquezInstitut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Ocular Inflammation Group, Barcelona, Spain.
Sergio RecaldeRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.
Jaione BezunarteaRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.
Maite Moreno OrduñaRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.
Idoia Belza-ZuazuRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.
Alfredo García-LayanaRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.
Alfredo AdánInstitut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Ocular Inflammation Group, Barcelona, Spain.
Patricia Fernández-Robredo *Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain. pfrobredo@unav.es.
Blanca Molins *Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Ocular Inflammation Group, Barcelona, Spain.

Funding

Advanced Therapies Network, RICORS-TERAV RD21/0017/0009Carlos III Health Institute and co-financed by the European Union RD24/0007/0015Inflammatory Diseases Network, RICORS-REI RD21/0002/0010Instituto de Salud Carlos III PI19/00265Red del complemento de la Comunidad de Madrid Complemento 2-CMRed del complemento y Salud SAF2016-81876-REDTRed Temática de Investigación Cooperativa en Salud, OFTARED RD16/0008
6 · The paper itself

Abstract

Choroidal neovascularization (CNV) and inflammation play an important role in retinal disease development and the acute phase reactant C-reactive protein (CRP) has been shown to contribute to Age-related macular degeneration (AMD) in vitro. Our aim was to evaluate whether monomeric and pentameric CRP (pCRP, mCRP) isoforms contribute to CNV in vivo and to characterize the mechanism of CRP dissociation in-vivo and in vitro. Both CRP isoforms were intravitreally (IVT) or intravenously (IV) injected in mice, CNV was laser-induced, retinography and fluorescein angiography were performed to evaluate edema. Lectin, mCRP, F4/80 and C5b9 localization were assessed by immunofluorescence and visualized under a confocal microscope. CNV, intensity of fluorescence of mCRP (IF mCRP) was also quantified. To confirm pCRP dissociation in RPE cells and mice, pCRP was coupled to a fluorochrome and IVT injected. A statistical increase in CNV areas was observed in pCRP IVT injected males (p < 0.05) while a statistical decrease was shown in females (p < 0.05). After IV injection, pCRP males showed an increase in CNV areas only vs. mCRP injected mice (p < 0.05) and in females the injection of pCRP injected mice showed higher CNV areas vs. vehicle (p < 0.05) and vs. mCRP injected mice (p < 0.05). Retinal edema after IVT CRP injection was observed mainly in mCRP injected mice. In females there was an IF mCRP statistical decrease in pCRP IVT injected mice vs. vehicle and a statistical increase in pCRP IV injected mice vs. vehicle (p < 0.05). Mice injected with IVT isoforms showed F4/80 positive cells and C5b-9 deposition around the CNV areas. mCRP labeling was observed in the intercellular space of the endothelial cells in the angiogenic area and detected in pCRP IVT injected animals, demonstrating the dissociation of pCRP into mCRP both in vitro and in vivo in proinflammatory microenvironments. In conclusion, CRP administration increased the area of CNV and the edema observed in the subretinal space, suggesting that CRP is activated in the CNV inflammatory environment. In addition, we demonstrated that pCRP dissociates in vivo into mCRP in damaged areas close to CNV, hypothesizing that the CNV process is exacerbated by mCRP.

Indexed as

Choroidal NeovascularizationC-Reactive ProteinMacular DegenerationAnimalsDisease Models, AnimalFemaleFluorescein AngiographyHumansMaleMiceMice, Inbred C57BLProtein IsoformsRetinal Pigment EpitheliumC-Reactive ProteinProtein IsoformsAge macular degenerationChoroidal neovascularizationComplement pathwayC-reactive proteinInflammationRetinal pigment epithelium

Identifiers

PMID40858941
PMCPMC12381139

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.