Data · study · 2026
ALKBH5 fuels angiogenesis and collagen deposition via m6A-YTHDF2-Dependent NLRP3 mRNA stabilization aggravating scarring after glaucoma surgery [MeRIP-seq]
Listed in NCBI GEO
Glaucoma is a leading cause of irreversible blindness.
Description
For patients unresponsive to medical therapy, glaucoma filtration surgery (GFS) is the primary intervention to lower intraocular pressure (IOP). However, postoperative scarring often causes surgical failure, and the mechanisms remain poorly defined.
Here, we identify the RNA demethylase alkB homolog 5 (ALKBH5) as a regulator of fibrotic remodeling after GFS via an epitranscriptomic mechanism involving N6-methyladenosine (m6A) modification. In both patients and rabbit models, increased vascular perfusion and decreased bleb height—quantified by anterior segment optical coherence tomography angiography (AS-OCTA) and ultrasound biomicroscopy (UBM)—were associated with elevated IOP.
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Immunohistochemistry and single-cell RNA sequencing revealed ALKBH5 upregulation in vascular endothelial cells (VECs) within scar tissue. Functional assays, rabbit GFS models, and Alkbh5-deficient mice revealed that ALKBH5 promotes angiogenesis and collagen deposition, accelerating postoperative fibrosis. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) identified NLR family pyrin domain containing 3 (NLRP3) as a downstream target of ALKBH5.
Mechanistically, ALKBH5 removes m6A modifications from NLRP3 mRNA, preventing YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated degradation and stabilizing its expression. These findings uncover a role of ALKBH5–YTHDF2–NLRP3 axis in GFS-induced fibrosis and suggest targeting this epitranscriptomic pathway in VECs may improve outcomes.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304419 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304419 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1301285 ncbi.nlm.nih.gov/bioproject/PRJNA1301285 ↗
project · from NCBI GEO
- PubMed 42218253 pubmed.ncbi.nlm.nih.gov/42218253 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Homo sapiens · Other
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE304419 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |