Cited by 14Retinal Diseases and TreatmentsComplement system in diseasesRetinal Development and Disorders

Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

Open access
Garland, Donita L., Pierce, Eric A., Fernandez-Godino, Rosario·2021·Scientific Reports

Published version of a preprint

Abstract

The complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1 -associated macular degeneration. In this study, we have used double mutant Efemp1 R345W/R345W : C5 -/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-021-89978-8

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 64 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Garland, D. L., Pierce, E. A., & Fernandez-Godino, R.
Affiliations
Massachusetts Eye and Ear Infirmary (US)
Venue
Scientific Reports
Published
2021-05-17
Volume
11
Issue
1
Pages
10416-10416
ISSN
2045-2322 (ISSN-L)
OpenAlex
W3162622393
Cited by
14
References
64
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3
FWCI
2.47
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Eye Institute (P30EY014104, P30EY003790)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Keywords
complement C5, age-related macular degeneration, EFEMP1, complement activation, C3 activation, complement dysregulation, retinal pigment epithelium, extracellular matrix turnover, matrix metalloproteinases, therapeutic target
MeSH terms
Animals, Complement Activation, Complement C5, Disease Models, Animal, Extracellular Matrix, Female, Humans, Male, Mutation, Retinal Degeneration, Extracellular Matrix Proteins, Mice, Knockout, Matrix Metalloproteinases, Mice, Retinal Pigment Epithelium

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review