Expression profile analysis to identify potential gene changes induced by dexamethasone in the trabecular meshwork

Abstract

AIM: To investigate potential gene changes in trabecular meshwork (TM) induced by dexamethasone (DEX) in steroid-induced glaucoma (SIG). METHODS: The expression data of 24 cases from a public functional genomics data were sorted to identify the mechanisms of action of DEX on the TM. The relationships of the differentially expressed genes (DEGs) were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the hub genes were screened by the Search Tool for the Retrieval of Interacting Genes Database (STRING) and Cytoscape tools. Finally, human TM cells (HTMCs) were treated with DEX to preliminarily explore the function of hub genes. RESULTS: Totally 47 DEGs, including 21 downregulated and 26 upregulated genes were identified. The primary enriched results of the DEGs consisted of inflammatory response, extracellular matrix (ECM), negative regulation of cell proliferation, TNF signalling pathway and the regulation of tryptophan channels by inflammatory mediators. Subsequently, pro-melanin-enriched hormone (PMCH) and Bradykinin B1 receptor (BDKRB1) were screened as hub genes. It is verified in GSE37474 data set. Western blot and quantitative real-time polymerase chain reaction (qPCR) results showed that protein and RNA expression levels of BDKRB1 were significantly decreased after DEX treatment, while PMCH was not significantly changed. CONCLUSION: BDKRB1 may be a key gene involved in SIG onset, providing a suitable therapeutic target for improving the prognosis of SIG patients.

Incident glaucoma and ocular hypertension after periocular and intravitreal steroid injections: a claims-based analysis

“…The prolonged action of steroids within the vitreous is especially notable for sustained-release implants such as Iluvien and Retisert, which deliver fluocinolone acetonide intraocularly for up to 36 months 23. While the exact mechanism of steroid-induced glaucoma is not yet fully elucidated, corticosteroids are hypothesised to interact with various enzymes and cytoskeletal components within the trabecular meshwork to cause increased aqueous outflow resistance and therefore elevated IOP 2 3. Studies have demonstrated that corticosteroids can lead to microstructure alterations within the trabecular meshwork through the upregulation of myocilin and through binding to glucocorticoid receptor beta 24 25.…”

“…The use of sustained-release steroid delivery devices—including injectable 0.7 mg dexamethasone and 0.19 mg fluocinolone acetonide intravitreal implants (Ozurdex and Iluvien, respectively) and surgically implantable 0.59 mg fluocinolone acetonide intravitreal tablets (Retisert)—has transformed the management of conditions such as macular oedema due to chronic non-infectious uveitis and various other etiologies 1. Ocular hypertension (OHT) and glaucoma are well-recognised complications of steroid administration due to possible microstructure alterations in the trabecular meshwork that lead to increased aqueous outflow resistance and elevated intraocular pressure (IOP) 2 3. In some cases, steroid-induced glaucoma can be vision-threatening and require management with topical, laser or even surgical intervention.…”