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Investigation of Conjunctival Fibrosis Response Using a 3D Glaucoma Tenon's Capsule + Conjunctival Model
Rachel Gater1, Tugce Ipek1, Salman Sadiq1
1Institute for Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, United Kingdom.
Investigative Ophthalmology & Visual Science
|February 7, 2019
Summary
Glaucoma surgery success may be improved by understanding how aqueous humor and shear stress affect tissue fibrosis. This study shows these factors increase cell proliferation and neocollagen synthesis in Tenon's capsule and conjunctival tissue models.
Area of Science:
- Ophthalmology
- Tissue Engineering
- Wound Healing Research
Background:
- Glaucoma surgery, like trabeculectomy, creates new aqueous humor drainage pathways but is limited by post-operative tissue fibrosis.
- Fibrosis in Tenon's capsule and conjunctival tissue (TCCT) impedes surgical success by obstructing fluid outflow.
- Understanding the cellular mechanisms driving fibrosis is crucial for improving glaucoma treatment outcomes.
Purpose of the Study:
- To investigate the synergistic effects of aqueous humor and shear stress on the fibrotic response in TCCT.
- To analyze the impact of key growth factors and mechanotransduction on fibroblast behavior in vitro.
- To quantify neocollagen synthesis as a marker of fibrosis in engineered TCCT models.
Main Methods:
- Development of 2D and 3D in vitro TCCT models using porcine fibroblasts in collagen gel.
- Assessment of fibroblast proliferation, actin expression, and metabolic activity under various conditions, including growth factors, aqueous humor, and shear stress.
- Utilized a non-destructive assay to quantify neocollagen synthesis over 14 days to validate fibrosis.
Main Results:
- Transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) significantly increased TCCT fibroblast proliferation.
- Exposure to 50% aqueous humor markedly enhanced fibroblast proliferation and actin expression.
- Shear stress promoted metabolic activity and appeared to amplify the fibrotic effects of growth factors.
Conclusions:
- Aqueous humor and shear stress play significant roles in promoting the fibrotic response within TCCT models.
- Findings provide insights into the wound-healing mechanisms following glaucoma surgery, particularly concerning aqueous fluid outflow.
- Further research into these factors may lead to strategies for mitigating fibrosis and enhancing glaucoma surgical outcomes.