Evidence mapPaperPMID 39457089Full record

ArticleInternational journal of molecular sciences2024

Proliferative Diabetic Retinopathy Microenvironment Drives Microglial Polarization and Promotes Angiogenesis and Fibrosis via Cyclooxygenase-2/Prostaglandin E2 Signaling.

Shuta Kishishita, Ayumi Usui-Ouchi, Yasuo Ouchi, Yuiko Hata, Nobuyuki Ebihara, Shintaro Nakao

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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

4 citing papers in PubMed.

  1. 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

6 authors.

Shuta KishishitaDepartment of Ophthalmology, Juntendo University Urayasu Hospital, 2-1-1 Urayasu, Chiba 279-0021, Japan.
Ayumi Usui-OuchiDepartment of Ophthalmology, Juntendo University Urayasu Hospital, 2-1-1 Urayasu, Chiba 279-0021, Japan.ORCID 0000-0003-2974-0830
Yasuo OuchiDepartment of Regenerative Medicine, Graduate School of Medicine, Chiba University, Chiba 263-8522, Japan.
Yuiko HataDepartment of Ophthalmology, Juntendo University Urayasu Hospital, 2-1-1 Urayasu, Chiba 279-0021, Japan.
Nobuyuki EbiharaDepartment of Ophthalmology, Juntendo University Urayasu Hospital, 2-1-1 Urayasu, Chiba 279-0021, Japan.
Shintaro NakaoDepartment of Ophthalmology, Juntendo University Graduate school of Medicine, 2-1-1 Bunkyo, Tokyo 113-8421, Japan.ORCID 0000-0003-4200-0052

Funding

JSPS KAKENHI Grant 22KK0291)
6 · The paper itself

Abstract

Diabetic retinopathy (DR) is the leading cause of visual impairment, particularly in the proliferative form (proliferative DR [PDR]). The impact of the PDR microenvironment on microglia, which are the resident immune cells in the central nervous system, and the specific pathological changes it may induce remain unclear. This study aimed to investigate the role of microglia in the progression of PDR under hypoxic and inflammatory conditions. We performed a comprehensive gene expression analysis using human-induced pluripotent stem cell-derived microglia under different stimuli (dimethyloxalylglycine (DMOG), lipopolysaccharide (LPS), and DMOG + LPS) to mimic the hypoxic inflammatory environment characteristic of PDR. Principal component analysis revealed distinct gene expression profiles, with 76 genes synergistically upregulated under combined stimulation. Notably, prostaglandin-endoperoxide synthase 2 (encoding cyclooxygenase (COX)-2) exhibited the most pronounced increase, leading to elevated prostaglandin E2 (PGE2) levels and driving pathological angiogenesis and inflammation via the COX-2/PGE2/PGE receptor 2 signaling axis. Additionally, the upregulation of the fibrogenic genes snail family transcriptional repressor 1 and collagen type I alpha 1 chain suggested a role for microglia in fibrosis. These findings underscore the critical involvement of microglia in PDR and suggest that targeting both the angiogenic and fibrotic pathways may present new therapeutic strategies for managing this condition.

Indexed as

Cyclooxygenase 2Diabetic RetinopathyDinoprostoneFibrosisMicrogliaNeovascularization, PathologicSignal TransductionAngiogenesisCell PolarityCellular MicroenvironmentHumansInduced Pluripotent Stem CellsReceptors, Prostaglandin E, EP2 SubtypeCyclooxygenase 2DinoprostoneReceptors, Prostaglandin E, EP2 SubtypeCOX-2diabetic retinopathyhuman microgliahypoxiainflammationneurovascular unit

Identifiers

PMID39457089
PMCPMC11508523

What Socratic 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 Socratic graph.