July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Assessing the effects of indomethacin and dexamethasone on wound healing using a 3D bioartificial tissue of human Tenon’s capsule fibroblasts
Author Affiliations & Notes
  • Jim Denstedt
    Schulich School of Medicine and Dentistry, London, Ontario, Canada
  • James Armstrong
    Schulich School of Medicine and Dentistry, London, Ontario, Canada
  • Cindy ML Hutnik
    Schulich School of Medicine and Dentistry, London, Ontario, Canada
    Ophthalmology, St. Joseph's Health Care, London, Ontario, Canada
  • Charles Trelford
    Schulich School of Medicine and Dentistry, London, Ontario, Canada
  • Footnotes
    Commercial Relationships   Jim Denstedt, None; James Armstrong, None; Cindy Hutnik, None; Charles Trelford, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 479. doi:
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      Jim Denstedt, James Armstrong, Cindy ML Hutnik, Charles Trelford; Assessing the effects of indomethacin and dexamethasone on wound healing using a 3D bioartificial tissue of human Tenon’s capsule fibroblasts. Invest. Ophthalmol. Vis. Sci. 2018;59(9):479.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To compare the effects of indomethacin, a non-steroidal anti-inflammatory drug (NSAID), and dexamethasone, on scarring outcomes in a 3D-bioartifical tissue (BAT) model of Tenon's capsule. Secondly, better understand the underlying mechanisms behind the antifibrotic effects of these drugs.

Methods : Human Tenon’s capsule fibroblasts (HTCFs) were cultured within collagen based tissue mimetics and treated with varying concentrations of indomethacin or dexamethacin for 7 days. Contraction of the collagen construct was measured over a 7-day period after which either total RNA was collected or the construct was fixed for histological staining. Real time quantitative PCR (qPCR) was performed to measure relative expression levels of 10 genes involved in the fibroproliferative response.

Results : Both drugs significantly reduced the contractile activity of HTCFs. The expression of ACTA2, the gene encoding alpha smooth muscle actin (aSMA), was significantly reduced in a dose dependent manner in the indomethacin group, compared to dexamethasone and control. RNA expression of the collagen encoding genes Col3A1 and Col2A1and of TBGFB1 were each reduced by the highest concentration of indomethacin. Fluorescent microscopy comparing relative expression of aSMA showed significantly reduced protein expression following indomethacin treatment, and significantly increased expression with dexamethasone treatment, compared to no treatment control (P<0.05).

Conclusions : The results of this study demonstrate the antifibrotic effects of NSAIDs in vitro on Tenon’s capsule fibroblasts. These results support a possible role of NSAIDs for antifibrotic therapy in glaucoma filtration surgery.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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