Investigation of Conjunctival Fibrosis Response Using a 3D Glaucoma Tenon's Capsule+ Conjunctival Model

Research output: Contribution to journalArticle

Authors

  • Rachel Gater
  • Tugce Ipek
  • Salman Sadiq
  • Dan Nguyen
  • Lynval Jones
  • Ying Yang

Colleges, School and Institutes

External organisations

  • Keele University

Abstract

Purpose: Surgical techniques such as trabeculectomy aim to treat glaucoma by making an incision into the scleral tissue, to create an alternative drainage pathway for aqueous to flow into the sub-Tenon's/subconjunctival space. However, tissue fibrosis and wound healing occurring after the procedures can reduce the success rate. This study aims to investigate the synergistic effects of aqueous humor in combination with shear stress on the fibrosis response occurring in Tenon's capsule and conjunctival tissue (TCCT) after glaucoma surgery.

Methods: Two-dimensional (2D) and 3D in vitro TCCT models were constructed by seeding porcine Tenon's capsule + conjunctival fibroblasts in collagen gel. These were used to investigate key growth factors (singular and natural form) with shear stress, which are believed to influence tissue fibrosis after glaucoma surgery. In addition to cell proliferation assessments, a nondestructive assay to quantify neocollagen synthesis in TCCT models, in response to these factors, has been applied up to 14 days.

Results: TCCT fibroblast proliferation increased significantly with doses of TGF-β, TNF-α, and VEGF, in comparison with the control. Furthermore, fibroblasts exposed to 50% aqueous humor had significantly increased proliferation and actin expression. Shear stress–induced mechanotransduction was also found to promote metabolic activity across experimental conditions. Neocollagen labeling cross validated the fibrosis process.

Conclusions: Shear stress appeared to enhance the influence of key growth factors and further promoted fibrotic response within the model. These findings offer a useful insight for further study into the wound-healing response triggered by aqueous fluid outflow after glaucoma surgery.

Details

Original languageEnglish
Pages (from-to)605-614
Number of pages10
JournalInvestigative Opthalmology & Visual Science
Volume60
Issue number2
Publication statusPublished - 28 Feb 2019

Keywords

  • 3d model, Conjunctiva, Fibrosis, Glaucoma, Tenon’s capsule