Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells

TL;DR

This study shows that BMP-7 can reduce harmful effects of steroids on eye cells, potentially preventing steroid-induced glaucoma.

Contribution

BMP-7 is shown to inhibit steroid-induced extracellular matrix accumulation in trabecular meshwork cells, suggesting a new therapeutic approach for glaucoma.

Findings

BMP-7 co-treatment significantly reduced ECM production in steroid-treated human trabecular meshwork cells.

BMP-7 modulated the expression of genes involved in ECM regulation.

BMP-7 shows protective, anti-fibrotic effects against steroid-induced ECM synthesis.

Abstract

Long‐term steroid use, though essential for treating eye diseases, can cause increased intraocular pressure (IOP) in susceptible individuals and may lead to steroid‐induced glaucoma in a subset of patients. This study investigated the effect of bone morphogenetic protein‐7 (BMP‐7) on steroid‐induced extracellular matrix (ECM) synthesis in human trabecular meshwork (TM) cells. We sought to explore the potential of BMP‐7 as a protective agent against steroid‐induced ECM accumulation in the TM. Human TM cells (HTMCs) were treated with either steroids alone or a combination of steroids and BMP‐7 to compare their effects on ECM production. BMP‐7, known for its transforming growth factor beta (TGF‐β) antagonistic properties, was administered using a micellized protein transduction domain (mPTD)‐fused BMP‐7 polypeptide to enhance activity. Gene expression analysis was conducted to identify specific genes involved in ECM regulation. BMP‐7 effectively inhibited steroid‐induced ECM accumulation in HTMCs. There was a significant reduction in ECM production in the steroid and BMP‐7 co‐treated group compared with that in the steroid‐only group. Furthermore, several genes involved in ECM regulation were identified in the co‐treatment, underscoring BMP‐7's potential role in modulating ECM metabolism. These findings demonstrate that BMP‐7 exerts protective, anti‐fibrotic effects in HTMCs by inhibiting steroid‐induced ECM synthesis. BMP‐7 may serve as a promising therapeutic target for preventing or treating steroid‐induced glaucoma by maintaining normal aqueous humor outflow and preventing IOP elevation.

Long‐term steroid use can elevate intraocular pressure (IOP) and lead to steroid‐induced glaucoma by promoting extracellular matrix (ECM) accumulation in the trabecular meshwork (TM). This study demonstrates that bone morphogenetic protein‐7 (BMP‐7), delivered via a micellized protein transduction domain (mPTD), effectively inhibits steroid‐induced ECM synthesis in human TM cells. BMP‐7 co‐treatment reduced ECM production and modulated ECM‐related gene expression, highlighting its potential as a therapeutic strategy to prevent steroid‐induced glaucoma.

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