Assessing the effects of indomethacin and dexamethasone on wound healing using a 3D bioartificial tissue of human Tenon’s capsule fibroblasts

Abstract Body:  

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. 

Study Design: An in vitro experiment comparing fibrotic outcomes of steroid and NSAID treatment on human Tenon’s capsule fibroblasts.

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.