Evidence map›Paper›PMID 35382832›Full record

ArticleJournal of neuroinflammation2022

Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis.

Caijiao Yi, Jian Liu, Wen Deng, Chang Luo, Jinyan Qi, Mei Chen, Heping Xu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
15.5field-weighted citation impact, top 1% 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

43 citing papers in PubMed, 68 citations in OpenAlex.

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  14. The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
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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

7 authors at 2 institutions in 2 countries.

Caijiao YiAier School of Ophthalmology, Central South University, Changsha, 410000, China.
Jian LiuAier Institute of Optometry and Vision Science, Changsha, 410000, China.
Wen DengAier School of Ophthalmology, Central South University, Changsha, 410000, China.
Chang LuoAier School of Ophthalmology, Central South University, Changsha, 410000, China.
Jinyan QiAier School of Ophthalmology, Central South University, Changsha, 410000, China.
Mei ChenThe Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Heping XuAier School of Ophthalmology, Central South University, Changsha, 410000, China. heping.xu@qub.ac.uk.
Central South University · CNQueen's University Belfast · GB

Funding

Fight for Sight UK 5057/5058; 5105/5106Hunan Provincial Natural Science Youth Found 2021JJ4002Hunan Science & Technology Association 2021KX001Science Research Foundation of Aier Eye Hospital Group AM1913D1, AR2003D1Science & Technology Department of Hunan Province 2018RS3123
6 · The paper itself

Abstract

backgroundMacular subretinal fibrosis is the end-stage complication of neovascular age-related macular degeneration (nAMD). We previously developed a mouse model of two-stage laser-induced subretinal fibrosis that mimics closely the dynamic course of macular fibrosis in nAMD patients. This study was aimed to understand the molecular mechanism of subretinal fibrosis.

methodsSubretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced protocol. Twenty days later, eyes were collected and processed for RNA sequencing (RNA-seq) analysis. DESeq2 was used to determine the differentially expressed genes (DEGs). Gene Ontology (GO) and KEGG were used to analyze the enriched pathways. The expression of the selected DEGs including Mmp12 was verified by qPCR. The expression of MMP12 in subretinal fibrosis of mouse and nAMD donor eyes was examined by immunofluorescence and confocal microscopy. The expression of collagen 1, αSMA and fibronectin and cytokines in bone marrow-derived macrophages from control and subretinal fibrosis mice were examined by qPCR, immunocytochemistry and Luminex multiplex cytokine assay. The MMP12 specific inhibitor MMP408 was used to evaluate the effect of MMP12 on TGFβ-induced macrophage-to-myofibroblast transition (MMT) in vitro and its role in subretinal fibrosis in vivo.

resultsRNA-seq analysis of RPE-choroid from subretinal fibrosis eyes uncovered 139 DEGs (fold change log2(fc) ≥ 0.5, FDR < 0.05), including 104 up-regulated and 35 were down-regulated genes. The top 25 enrichment GO terms were related to inflammation, blood vessels/cardiovascular development and angiogenesis. One of the most significantly upregulated genes, Mmp12, contributed to 12 of the top 25 GO terms. Higher levels of MMP12 were detected in subretinal fibrotic lesions in nAMD patients and the mouse model, including in F4/80

conclusionsMMP12 critically contributes to the development of subretinal fibrosis, partially through promoting MMT.

Indexed as

Matrix Metalloproteinase 12RetinaAnimalsFibrosisHumansMiceMice, Inbred C57BLmatrix metallopeptidase 12, mouseMatrix Metalloproteinase 12Age-related macular degenerationInflammationMacular fibrosisMatrix metalloproteinase-12RNA sequencing

Identifiers

PMID35382832
PMCPMC8985356
OpenAlexW4223498358

What OpenQuestion holds

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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.