Evidence map›Paper›PMID 29392311›Full record

ArticleInvestigative ophthalmology & visual science2018

Effect of Anti-C5a Therapy in a Murine Model of Early/Intermediate Dry Age-Related Macular Degeneration.

Christopher B Toomey, Michael Landowski, Mikael Klingeborn, Una Kelly, John Deans, Holly Dong, Ons Harrabi, Thomas Van Blarcom, Yik Andy Yeung, Ruslan Grishanin and 3 more

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.2field-weighted citation impact, top 9% of its field
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

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Modeling complex age-related eye disease.Progress in retinal and eye research · 2024
    Review
  6. Article
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  8. Article
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  13. Review
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  15. Article
  16. Targeting Lipid Metabolism for the Treatment of Age-Related Macular Degeneration: Insights from Preclinical Mouse Models.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
    Review
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

13 authors at 4 institutions in 1 country.

Christopher B ToomeyDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Michael LandowskiDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Mikael KlingebornDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Una KellyDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
John DeansDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Holly DongRinat, Pfizer Inc, South San Francisco, California, United States.
Ons HarrabiRinat, Pfizer Inc, South San Francisco, California, United States.
Thomas Van BlarcomRinat, Pfizer Inc, South San Francisco, California, United States.
Yik Andy YeungRinat, Pfizer Inc, South San Francisco, California, United States.
Ruslan GrishaninRinat, Pfizer Inc, South San Francisco, California, United States.
John C LinRinat, Pfizer Inc, South San Francisco, California, United States.
Daniel R SabanDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Catherine Bowes RickmanDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Pfizer (United States) · USDuke Medical Center · USDuke University Hospital · USUniversity of California, San Diego · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
Medical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6M
Innate immunity, lipoproteins and AMD progressionR01EY026161 · NEI · DUKE UNIVERSITY · PI BOWES RICKMAN, CATHERINE · 2016 to 2019
$2.0M
NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY026161NIGMS NIH HHS T32 GM007171NIGMS NIH HHS T32 GM145449
6 · The paper itself

Abstract

Purpose: A large body of evidence supports a central role for complement activation in the pathobiology of age-related macular degeneration (AMD), including plasma complement component 5a (C5a). Interestingly, C5a is a chemotactic agent for monocytes, a cell type also shown to contribute to AMD. However, the role monocytes play in the pathogenesis of "dry" AMD and the pharmacologic potential of targeting C5a to regulate these cells are unclear. We addressed these questions via C5a blockade in a unique model of early/intermediate dry AMD and large panel flow cytometry to immunophenotype monocytic involvement. Methods: Heterozygous complement factor H (Cfh+/-) mice aged to 90 weeks were fed a high-fat, cholesterol-enriched diet (Cfh+/-∼HFC) for 8 weeks and were given weekly intraperitoneal injections of 30 mg/kg anti-C5a (4C9, Pfizer). Flow cytometry, retinal pigmented epithelium (RPE) flat mounts, and electroretinograms were used to characterize anti-C5a treatment. Results: Aged Cfh+/- mice developed RPE damage, sub-RPE basal laminar deposits, and attenuation of visual function and immune cell recruitment to the choroid that was accompanied by expression of inflammatory and extracellular matrix remodeling genes following 8 weeks of HFC diet. Concomitant systemic administration of an anti-C5a antibody successfully inhibited local recruitment of mononuclear phagocytes to the choroid-RPE interface but did not ameliorate these AMD-like pathologies in this mouse model. Conclusions: These results show that immunotherapy targeting C5a is not sufficient to block the development of the AMD-like pathologies observed in Cfh+/-∼HFC mice and suggest that other complement components or molecules/mechanisms may be driving "early" and "intermediate" AMD pathologies.

Indexed as

Disease Models, AnimalImmunotherapyAnimalsAntibodies, BlockingCholesterol, DietaryChoroidal NeovascularizationComplement ActivationComplement C5aElectroretinographyEnzyme-Linked Immunosorbent AssayFlow CytometryGeographic AtrophyInjections, IntraperitonealMaleMiceMice, Inbred C57BL4C9 antibody, ratAntibodies, BlockingCholesterol, DietaryComplement C5a

Identifiers

PMID29392311
PMCPMC5795897
OpenAlexW2785786028

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.