Evidence map›Paper›PMID 36428965›Full record

ArticleCells2022

Microglia-Neutrophil Interactions Drive Dry AMD-like Pathology in a Mouse Model.

Maeve Boyce, Ying Xin, Olivia Chowdhury, Peng Shang, Haitao Liu, Victoria Koontz, Anastasia Strizhakova, Mihir Nemani, Stacey Hose, J Samuel Zigler and 6 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. VEGF in Diabetic Retinopathy and Age-Related Macular Degeneration.International journal of molecular sciences · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Neutrophils in Ocular Diseases.International journal of molecular sciences · 2024
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Lysosomes in retinal health and disease.Trends in neurosciences · 2023
    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

16 authors at 4 institutions in 3 countries.

Maeve BoyceDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Ying XinDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Olivia ChowdhuryDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Peng ShangDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Haitao LiuDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.ORCID 0000-0002-3757-779X
Victoria KoontzDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Anastasia StrizhakovaDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Mihir NemaniDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Stacey HoseDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Samuel ZiglerDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Matthew CampbellSmurfit Institute of Genetics, Trinity College, D02 PN40 Dublin, Ireland.
Debasish SinhaDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
James T HandaDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Kai KaarnirantaDepartment of Ophthalmology, Kuopio University Hospital, University of Eastern Finland, 70211 Kuopio, Finland.ORCID 0000-0003-2600-8679
Jiang QianDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Sayan GhoshDepartment of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
University of Pittsburgh · USJohns Hopkins University · USTrinity College Dublin · IEUniversity of Eastern Finland · FI

Funding

Targeting lysosome/RPE heterogeneity in AMD pathobiology as a novel therapyR01EY031594 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HANDA, JAMES T, SINHA, DEBASISH · 2021 to 2024
$2.4M
NEI NIH HHS R01 EY031594NEI NIH HHS R01EY031594
6 · The paper itself

Abstract

In dry age-related macular degeneration (AMD), inflammation plays a key role in disease pathogenesis. Innate immune cells such as microglia and neutrophils infiltrate the sub-retinal space (SRS) to induce chronic inflammation and AMD progression. But a major gap in our understanding is how these cells interact with each other in AMD. Here, we report a novel concept of how dynamic interactions between microglia and neutrophils contribute to AMD pathology. Using well-characterized genetically engineered mouse models as tools, we show that in the diseased state, retinal pigmented epithelial (RPE) cells trigger pro-inflammatory (M1) transition in microglia with diminished expression of the homeostatic marker, CX3CR1. Activated microglia localize to the SRS and regulate local neutrophil function, triggering their activation and thereby inducing early RPE changes. Ligand receptor (LR)-loop analysis and cell culture studies revealed that M1 microglia also induce the expression of neutrophil adhesion mediators (integrin β1/α4) through their interaction with CD14 on microglia. Furthermore, microglia-induced neutrophil activation and subsequent neutrophil-mediated RPE alterations were mitigated by inhibiting Akt2 in microglia. These results suggest that the Akt2 pathway in microglia drives M1 microglia-mediated neutrophil activation, thereby triggering early RPE degeneration and is a novel therapeutic target for early AMD, a stage without treatment options.

Indexed as

Macular DegenerationNeutrophilsAnimalsDisease Models, AnimalInflammationMiceMicrogliaage-related macular degenerationAkt2CD14chronic inflammationintegrin α4integrin β1LR-loopmicroglianeutrophilsretinal pigmented epithelial cells

Identifiers

PMID36428965
PMCPMC9688699
OpenAlexW4308866504

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.