ArticleInternational journal of molecular sciences2021
Sodium 4-Phenylbutyrate Reduces Ocular Hypertension by Degrading Extracellular Matrix Deposition via Activation of MMP9.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Transcending genome-wide association studies to create useful multi-omic views of glaucoma.Progress in retinal and eye research · 2026Review
- Pharmacological restoration of impaired autophagy in retinal ganglion cells prevents abnormal mitochondrial accumulation and glaucomatous neurodegeneration.Molecular neurodegeneration · 2026Article
- C/EBP Homologous Protein Expression in Retinal Ganglion Cells Induces Neurodegeneration in Mice.International journal of molecular sciences · 2025Article
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025Review
- Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.Investigative ophthalmology & visual science · 2024Article
- Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis.Frontiers in molecular biosciences · 2024Article
- Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?Antioxidants (Basel, Switzerland) · 2023Review
- Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.iScience · 2022Article
- Genome-Wide RNA Sequencing of Human Trabecular Meshwork Cells Treated with TGF-β1: Relevance to Pseudoexfoliation Glaucoma.Biomolecules · 2022Article
- The Intertwined Roles of Oxidative Stress and Endoplasmic Reticulum Stress in Glaucoma.Antioxidants (Basel, Switzerland) · 2022Review
- The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms.International journal of molecular sciences · 2022Review
- Mechanism underlying circRNA dysregulation in the TME of digestive system cancer.Frontiers in immunology · 2022Review
- Astragaloside IV Attenuates Ocular Hypertension in a Mouse Model of TGFβ2 Induced Primary Open Angle Glaucoma.International journal of molecular sciences · 2021Article
- The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma - a literature review.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologieReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ocular hypertension (OHT) is a serious adverse effect of the widely prescribed glucocorticoid (GC) therapy and, if left undiagnosed, it can lead to glaucoma and complete blindness. Previously, we have shown that the small chemical chaperone, sodium-4-phenylbutyrate (PBA), rescues GC-induced OHT by reducing ocular endoplasmic reticulum (ER) stress. However, the exact mechanism of how PBA rescues GC-induced OHT is not completely understood. The trabecular meshwork (TM) is a filter-like specialized contractile tissue consisting of TM cells embedded within extracellular matrix (ECM) that controls intraocular pressure (IOP) by constantly regulating aqueous humor (AH) outflow. Induction of abnormal ECM deposition in TM is a hallmark of GC-induced OHT. Here, we investigated whether PBA reduces GC-induced OHT by degrading abnormal ECM deposition in TM using mouse model of GC-induced OHT, ex vivo cultured human TM tissues and primary human TM cells. We show that topical ocular eye drops of PBA (1%) significantly lowers elevated IOP in mouse model of GC-induced OHT. Importantly, PBA prevents synthesis and deposition of GC-induced ECM in TM. We report for the first time that PBA can degrade existing abnormal ECM in normal human TM cells/tissues by inducing matrix metalloproteinase (MMP)9 expression and activity. Furthermore, inhibition of MMPs activity by chemical-inhibitor (minocycline) abrogated PBA's effect on ECM reduction and its associated ER stress. Our study indicates a non-chaperone activity of PBA via activation of MMP9 that degrades abnormal ECM accumulation in TM.
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Registered trials
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.