Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma

Alex Zhavoronkov, Riya R. Kanherkar, Evgeny Izumchenko, Mahder Teka, Charles Cantor, Kebreten Manaye, David Sidransky, Michael D. West, Eugene Makarev, Antonei Benjamin Csoka

Research output: Contribution to journalArticlepeer-review

Abstract

ABSTRACT: While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues.

Original languageEnglish (US)
Pages (from-to)1643-1652
Number of pages10
JournalCell Cycle
Volume15
Issue number12
DOIs
StatePublished - Jun 17 2016
Externally publishedYes

Keywords

  • POAG
  • TGFβ
  • fibrosis
  • glaucoma
  • lamina cribrosa
  • trabecular meshwork

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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