4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model
- 1Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Key Laboratory of Intelligent Diagnosis Technology and Equipment for Optic Nerve-Related Eye Diseases, Capital Medical University
- 2State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology
- 3National Engineering Research Center for Rare Earth, Grirem Advanced Materials Co., Ltd.
Abstract
Purpose To develop a mesoporous silica nanoparticle-based delivery system for 4-phenylbutyric acid (4-PBA) and evaluate its potential to alleviate endoplasmic reticulum (ER) stress and improve mutant myocilin (MYOC)-associated glaucoma. Materials and methods We synthesized hollow/snowflake-like mesoporous silica nanoparticles loaded with 4-PBA (mSiO₂-PBA) for drug loading and release. Cellular uptake and cytotoxicity were evaluated in human corneal epithelial cells (HCECs) and human trabecular meshwork cells (HTMCs). The effects of mSiO₂-PBA on mutant MYOC secretion and ER stress-associated proteins were assessed by Western blot analysis. In Tg-MYOCN450Y mice, ocular distribution of mSiO₂-PBA was examined by fluorescence imaging and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Therapeutic efficacy was evaluated by intraocular pressure (IOP) measurements, immunofluorescence analysis of MYOC accumulation and ER stress-associated markers in trabecular meshwork tissue, and transmission electron microscopy (TEM). Results mSiO₂-PBA exhibited efficient cellular uptake and favorable biocompatibility in vitro. Treatment with mSiO₂-PBA enhanced mutant MYOC secretion and reduced ER stress-associated KDEL-positive proteins in HTMCs. Following topical administration, mSiO₂-PBA achieved ocular penetration and exposure in trabecular meshwork tissue. In Tg-MYOCN450Y mice, mSiO₂-PBA significantly reduced IOP, decreased mutant MYOC accumulation, and improved ER ultrastructural abnormalities in trabecular meshwork cells. Conclusions mSiO₂-PBA represents a promising nanoparticle-based delivery platform for 4-PBA in MYOC-associated glaucoma. By promoting mutant MYOC secretion and alleviating ER stress, mSiO₂-PBA demonstrated therapeutic efficacy in vitro and in vivo, supporting its potential as a nanotherapeutic strategy for MYOC-associated glaucoma.
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BibTeX
@article{yan20264phenylbutyric,
title = {{4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model}},
author = {Xuejing Yan and Wu Qin and Xiaoming Gan and Yingyan Mao and Shen Wu and Shipeng Wen and Jingxue Zhang},
journal = {Biology Direct},
year = {2026},
month = jul,
doi = {10.1186/s13062-026-00907-z},
url = {https://doi.org/10.1186/s13062-026-00907-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - 4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model
AU - Xuejing Yan
AU - Wu Qin
AU - Xiaoming Gan
AU - Yingyan Mao
AU - Shen Wu
AU - Shipeng Wen
AU - Jingxue Zhang
PY - 2026
DA - 2026/07/01
JO - Biology Direct
DO - 10.1186/s13062-026-00907-z
UR - https://doi.org/10.1186/s13062-026-00907-z
AB - Purpose To develop a mesoporous silica nanoparticle-based delivery system for 4-phenylbutyric acid (4-PBA) and evaluate its potential to alleviate endoplasmic reticulum (ER) stress and improve mutant myocilin (MYOC)-associated glaucoma. Materials and methods We synthesized hollow/snowflake-like mesoporous silica nanoparticles loaded with 4-PBA (mSiO₂-PBA) for drug loading and release. Cellular uptake and cytotoxicity were evaluated in human corneal epithelial cells (HCECs) and human trabecular meshwork cells (HTMCs). The effects of mSiO₂-PBA on mutant MYOC secretion and ER stress-associated proteins were assessed by Western blot analysis. In Tg-MYOCN450Y mice, ocular distribution of mSiO₂-PBA was examined by fluorescence imaging and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Therapeutic efficacy was evaluated by intraocular pressure (IOP) measurements, immunofluorescence analysis of MYOC accumulation and ER stress-associated markers in trabecular meshwork tissue, and transmission electron microscopy (TEM). Results mSiO₂-PBA exhibited efficient cellular uptake and favorable biocompatibility in vitro. Treatment with mSiO₂-PBA enhanced mutant MYOC secretion and reduced ER stress-associated KDEL-positive proteins in HTMCs. Following topical administration, mSiO₂-PBA achieved ocular penetration and exposure in trabecular meshwork tissue. In Tg-MYOCN450Y mice, mSiO₂-PBA significantly reduced IOP, decreased mutant MYOC accumulation, and improved ER ultrastructural abnormalities in trabecular meshwork cells. Conclusions mSiO₂-PBA represents a promising nanoparticle-based delivery platform for 4-PBA in MYOC-associated glaucoma. By promoting mutant MYOC secretion and alleviating ER stress, mSiO₂-PBA demonstrated therapeutic efficacy in vitro and in vivo, supporting its potential as a nanotherapeutic strategy for MYOC-associated glaucoma.
SN - 1745-6150
ER -