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Src mediates TGF-β-induced intraocular pressure elevation in glaucoma.

Teruhisa Tsukamoto1,2, Kentaro Kajiwara1, Shigeyuki Nada1

  • 1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

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|August 26, 2018
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Summary

Src kinase plays a key role in transforming growth factor-β (TGF-β)-induced elevation of intraocular pressure (IOP), a major glaucoma risk factor. Inhibiting Src signaling may offer a new therapeutic strategy for glaucoma treatment.

Keywords:
CasLSrcTGF-βglaucomatrabecular meshwork

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Cell Biology

Background:

  • Glaucoma is a leading cause of irreversible vision loss worldwide.
  • Elevated intraocular pressure (IOP) is a primary risk factor for glaucoma.
  • The molecular mechanisms linking transforming growth factor-β (TGF-β) to IOP elevation are not fully understood.

Purpose of the Study:

  • To investigate the role of Src kinase in TGF-β-induced intraocular pressure (IOP) elevation.
  • To explore Src signaling as a potential therapeutic target for glaucoma.

Main Methods:

  • Utilized dasatinib, a Src inhibitor, in rat models to assess IOP.
  • Performed mechanistic studies in human trabecular meshwork cells.
  • Analyzed TGF-β2-induced changes in cytoskeletal remodeling, cell adhesion, and extracellular matrix (ECM) accumulation.

Main Results:

  • Dasatinib suppressed TGF-β2-induced IOP elevation in rats.
  • TGF-β2 activated Src signaling in trabecular meshwork cells, leading to increased cytoskeletal remodeling, cell adhesion, and ECM accumulation.
  • Src activation suppressed tissue plasminogen activator expression, reducing ECM degradation.
  • Src inhibition ameliorated TGF-β2-induced alterations in cell contractility, adhesion, and ECM deposition.

Conclusions:

  • Src kinase is critically involved in TGF-β-induced IOP elevation.
  • Src signaling pathways mediate key cellular changes contributing to increased IOP.
  • Targeting Src signaling presents a promising therapeutic avenue for managing glaucoma.