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Integrin-Linked Kinase Suppression Reduces SPARC's Effect on Intraocular Pressure and Extracellular Matrix

Charles W Guo1, Seth Birrell1, Sophie Baillargeon1

  • 1Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States.

Investigative Ophthalmology & Visual Science
|August 21, 2026
PubMed
Abstract

Insights

Secreted protein acidic rich in cysteine (SPARC) increases intraocular pressure (IOP) by altering extracellular matrix (ECM) in the trabecular meshwork (TM). Inhibiting integrin-linked kinase (ILK) reduces SPARC-induced IOP elevation and ECM changes.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Biochemistry

Background:

  • The molecular mechanisms driving increased outflow resistance and intraocular pressure (IOP) in the trabecular meshwork (TM) are not fully understood.
  • Secreted protein, acidic and rich in cysteine (SPARC) is implicated in regulating IOP and extracellular matrix (ECM) organization in various tissues.
  • SPARC's interaction with integrin-linked kinase (ILK) is known to influence ECM organization in other biological contexts.

Purpose of the Study:

  • To investigate the role of SPARC in regulating ECM proteins within the TM.
  • To determine if SPARC influences TM ECM organization partly through the ILK signaling pathway.
  • To test the hypothesis that SPARC regulates ECM proteins via ILK in the TM.

Main Methods:

  • Overexpression of SPARC using Ad.SPARC and inhibition of ILK using shILK in mice, human TM cells, and human cadaveric anterior segments.
  • Measurement of IOP in mice and human anterior segments.
  • Analysis of ECM protein levels via immunoblotting and immunostaining.

Main Results:

  • SPARC overexpression significantly increased IOP in mice and human anterior segments.
  • Inhibition of ILK attenuated the SPARC-induced IOP elevation in both models.
  • SPARC overexpression led to increased levels of ECM proteins, including laminin, collagen I, and collagen VI, which were reduced by ILK inhibition in human TM cells.

Conclusions:

  • Integrin-linked kinase (ILK) signaling appears to mediate the effects of SPARC on IOP and ECM homeostasis in the TM.
  • ILK inhibition can counteract the detrimental effects of SPARC overexpression on TM physiology.
  • Further research into downstream transcription factors may elucidate the complete pathway involved in SPARC-mediated TM dysfunction and primary open-angle glaucoma (POAG) pathogenesis.

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