Co-delivery of ripasudil and dexamethasone in trabecular meshwork cells for potential prevention of GC-induced ocular hypertension

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-09-17 DOI:10.1016/j.yexcr.2025.114759

Tilahun Ayane Debele , Yong Yuan , Winston Kao , Chia-Yang Liu , Eskezeia Y. Dessie , Yoonjee C. Park

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Abstract

The purpose of this in vitro study is to investigate whether the co-delivery of Ripasudil (Rip) can suppress the expression of genes related to glaucoma pathogenesis induced by prolonged dexamethasone (Dex) use, which can lead to ocular hypertension and potentially glaucoma formation. The effects of Rip (10 μM) on Dex (100 nM)-treated human trabecular meshwork (TM) cells were tested through co-delivery and sequential treatments using RNA-seq. Genome-wide analysis was performed using gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with Enrichr and DAVID gene analysis tools. Gene enrichment and pathway analysis revealed that Rip, when co-delivered or sequentially delivered with Dex, influenced genes involved in glaucoma-related pathways such as focal adhesion, extracellular matrix (ECM) organization, and regulation of the actin cytoskeleton. Rip treatment downregulated genes like ACTA2, COL11A1, ECM2, MBP, and ANGPTL7, which are associated with increased outflow resistance and elevated intraocular pressure (IOP). Additionally, Rip upregulated ITGA11, a gene that promotes actin cytoskeleton reorganization and TM cell relaxation by inhibiting the Rho-ROCK pathway. Overall, co-delivery or sequential delivery of Rip can reverse or prevent Dex-induced ocular hypertension and glaucoma formation by modulating the expression of glaucoma-related genes at the transcriptional level.

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利帕舒地尔和地塞米松在小梁网细胞中共同递送可能预防气相色谱诱导的高眼压。

本体外研究的目的是探讨利帕舒地尔（Rip）合用是否能抑制长期使用地塞米松（Dex）引起的青光眼发病相关基因的表达，地塞米松可导致高眼压并可能形成青光眼。采用RNA-seq技术，通过共递送和顺序处理的方法检测Rip （10 μM）对Dex （100 nM）处理的人小梁网（TM）细胞的影响。使用基因本体（GO）富集和京都基因与基因组百科全书（KEGG）途径分析，使用enrichment和DAVID基因分析工具进行全基因组分析。基因富集和通路分析显示，Rip与Dex共递送或顺序递送时，影响了参与青光眼相关通路的基因，如局灶黏附、细胞外基质（ECM）组织和肌动蛋白细胞骨架的调节。Rip治疗下调ACTA2、COL11A1、ECM2、MBP和ANGPTL7等基因，这些基因与流出阻力增加和眼压升高有关。此外，Rip上调ITGA11，该基因通过抑制Rho-ROCK途径促进肌动蛋白细胞骨架重组和TM细胞松弛。总的来说，共给药或顺序给药Rip可以在转录水平上通过调节青光眼相关基因的表达来逆转或预防dex诱导的高眼压和青光眼的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.