Evidence mapPaperPMID 40111356Full record

ArticleInvestigative ophthalmology & visual science2025

Differential Roles of Macrophages and Microglia in Subretinal Fibrosis Secondary to Neovascular Age-Related Macular Degeneration.

Manon Szczepan, María Llorián-Salvador, Caijiao Yi, David Hughes, Matthias Mack, Mei Chen, Heping Xu

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Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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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

5 citing papers in PubMed.

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4 · The record

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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

7 authors.

Manon SzczepanQueen's University Belfast, School of Medicine Dentistry and Biomedical Sciences, Belfast, Belfast, United Kingdom.
María Llorián-SalvadorQueen's University Belfast, School of Medicine Dentistry and Biomedical Sciences, Belfast, Belfast, United Kingdom.
Caijiao YiAier Eye Institute, Aier Academy of Ophthalmology, Changsha Aier Eye Hospital, Hunan, China.
David HughesQueen's University Belfast, School of Medicine Dentistry and Biomedical Sciences, Belfast, Belfast, United Kingdom.
Matthias MackDepartment of Internal Medicine II - Nephrology, Universitatsklinikum Regensburg Klinik und Poliklinik Innere Medizin II, Regensburg, Bayern, Germany.
Mei ChenQueen's University Belfast, School of Medicine Dentistry and Biomedical Sciences, Belfast, Belfast, United Kingdom.
Heping XuQueen's University Belfast, School of Medicine Dentistry and Biomedical Sciences, Belfast, Belfast, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: To investigate the differential role of infiltrating CCR2+ macrophages and CX3CR1+ microglia in neovascular AMD (nAMD)-mediated subretinal fibrosis. Methods: Subretinal fibrosis was induced using the two-stage laser protocol in C57BL/6J or CX3CR1gfp/+ mice. The fibrotic lesion was detected using collagen-1 staining in retinal pigment epithelial /choroidal flatmounts. Infiltrating macrophages and microglial were identified using F4/80, CCR2, and CX3CR1 markers at one, three, six, and 10 days after the second laser. Circulating CCR2+ monocytes were depleted using the MC-21 antibody, whereas CX3CR1+ microglia were depleted using PLX5622. BV2 microglia were treated with TGF-β1 for 96 hours, and their profibrotic potential was examined by quantitative PCR and immunocytochemistry. Results: Subretinal fibrosis lesions developed three days after the second laser, accompanied by persistent CCR2+F4/80+ macrophage and CX3CR1+ cell infiltration. Inflammation in the first three days after the second laser was dominated by filtrating CX3CR1+ cells, and the number increased until day (D) 10 post-second laser. Depletion of CCR2+ monocytes from D5-10 significantly reduced the vascular and fibrotic components of the lesion, while CX3CR1+ cell depletion reduced Isolectin B4+ but not collagen-1+ lesion size. Bone marrow-derived macrophages from D6 and D10 mice expressed significantly higher levels of α-smooth muscle actin (α-SMA) and collagen-1 compared to cells from D1 and D3. TGFβ1 treatment increased TMEM119, CX3CR1, IL1b and iNOS gene expression but did not affect Acta2 and Col1a1 gene expression in BV2 cells. Conclusions: CCR2+ monocytes, but not CX3CR1+ microglia, critically contribute to the development of subretinal fibrosis in nAMD.

Indexed as

MacrophagesMacular DegenerationMicrogliaRetinaWet Macular DegenerationAnimalsChoroidal NeovascularizationCX3C Chemokine Receptor 1Disease Models, AnimalFibrosisImmunohistochemistryMiceMice, Inbred C57BLMonocytesReal-Time Polymerase Chain ReactionReceptors, CCR2Ccr2 protein, mouseCX3C Chemokine Receptor 1Cx3cr1 protein, mouseReceptors, CCR2

Identifiers

PMID40111356
PMCPMC11932421

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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 Socratic graph.