Fibrotic changes to schlemm’s canal endothelial cells in glaucoma

Ruth A. Kelly, Kristin M. Perkumas, Matthew Campbell, G. Jane Farrar, W. Daniel Stamer, Pete Humphries, Jeffrey O’ Callaghan, Colm J. O’brien

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Previous studies have shown that glaucomatous Schlemm’s canal endothelial cells (gSCECs) are stiffer and associated with reduced porosity and increased extracellular matrix (ECM) material compared to SCECs from healthy individuals. We hypothesised that Schlemm’s canal (SC) cell stiffening was a function of fibrotic changes occurring at the inner wall of SC in glaucoma. This study was performed in primary cell cultures isolated from the SC lumen of human donor eyes. RNA and protein quantification of both fibrotic and endothelial cell markers was carried out on both healthy and gSCECs. Functional assays to assess cell density, size, migration, proliferation, and mitochondrial function of these cells were also carried out. Indeed, we found that gSCECs deviate from typical endothelial cell characteristics and exhibit a more fibrotic phenotype. For example, gSCECs expressed significantly higher protein levels of the fibrotic markers α-SMA, collagen I-α1, and fibronectin, as well as significantly increased protein expression of TGFβ-2, the main driver of fibrosis, compared to healthy SCECs. Interestingly, we observed a significant increase in protein expression of endothelial marker VE-cadherin in gSCECs, compared to healthy SCECs. gSCECs also appeared to be significantly larger, and surprisingly proliferate and migrate at a significantly higher rate, as well as showing significantly reduced mitochondrial activity, compared to healthy SCECs.

Original languageEnglish (US)
Article number9446
JournalInternational journal of molecular sciences
Volume22
Issue number17
DOIs
StatePublished - Sep 1 2021
Externally publishedYes

Keywords

  • Endothelial cells
  • Endothelial–mesenchymal tran-sition
  • Fibrosis
  • Glaucoma
  • Proliferation
  • Schlemm’s canal

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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