Evidence map›Paper›PMID 41642026›Full record

ArticleInvestigative ophthalmology & visual science2026

The Molecular Mechanisms and Therapeutic Potentials of Engrailed-1 in Fibrotic Scar Formation Post Glaucoma Filtration Surgery.

Yi Lin, Wangdu Luo, Xiaomin Zhu, Julong Yu, Xiangji Li, Lin Xie

Abstract read
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Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yi LinDepartment of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wangdu LuoDepartment of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiaomin ZhuDepartment of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Julong YuDepartment of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiangji LiDepartment of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Lin XieDepartment of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Conjunctival scarring is a major cause of glaucoma filtration surgery (GFS) failure, necessitating effective antifibrotic strategies. This study investigated the role of engrailed-1 (EN1) in conjunctival fibrosis and evaluated the therapeutic potential of EN1-targeted biomaterials for antiscarring in post-GFS patients. Methods: Fibrotic models were developed using TGF-β2-induced human Tenon fibroblasts (HTFs) and a rat GFS model. EN1 was identified as a key therapeutic target using RNA interference, transcriptome sequencing, chromatin immunoprecipitation-qPCR, and dual-luciferase assays. Exosomes (Exos) loaded with EN1 small interfering RNA were encapsulated in a GelMA hydrogel to form the Gel-Exo-siEN1 composite material. Results: EN1 expression was significantly elevated in TGF-β2-stimulated HTFs and conjunctival scar tissue post GFS. Inhibition of EN1 reduced TGF-β2-induced proliferation and migration in HTFs and decreased fibrosis-related gene expression. These effects may be mediated through the Yes-related protein/transcriptional co-activator PDZ-binding motif and SMAD3 pathways. Assays confirmed that EN1 inhibition suppressed proliferation and migration and downregulated fibrosis markers like fibronectin, collagen I, and α-smooth muscle actin. Western blot analysis showed increased Yes-related protein/transcriptional co-activator PDZ-binding motif expression after TGF-β2 induction, which was reduced by verteporfin. Chromatin immunoprecipitation-PCR confirmed that SMAD3 binds to the EN1 promoter, regulating its expression. Exo analysis showed Exo-siEN1 maintained stability and effectively delivered siEN1, leading to significant EN1 knockdown and reduced fibrosis in rat Tenon's fibroblasts. Gel-Exo-siEN1 treatment significantly increased functional bleb area, reduced IOP, and decreased collagen deposition and inflammatory cell infiltration in the conjunctiva after GFS. Conclusions: Gel-Exo-siEN1 is a promising strategy for preventing postsurgical scarring and improving the outcomes of glaucoma surgery.

Indexed as

CicatrixConjunctival DiseasesFiltering SurgeryGene Expression RegulationGlaucomaHomeodomain ProteinsAnimalsBlotting, WesternCell MovementCell ProliferationCells, CulturedChromatin ImmunoprecipitationConjunctivaDisease Models, AnimalFibroblastsFibrosisHomeodomain ProteinsRNA, Small Interfering

Identifiers

PMID41642026
PMCPMC12889168

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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.