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Anuj Bharat Vakharia, Gurpreet Chouhan, Georgios Vakros, Ann Logan, Graham R Wallace, Saaeha Rauz; The Role of Decorin in Corneal Fibrotic Pathways. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3526.
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© ARVO (1962-2015); The Authors (2016-present)
The ocular surface (OcS) environment has evolved to limit inflammation in order to maintain optical clarity through mechanisms delivered by a highly specialised and rapidly self-renewing ocular mucosal barrier (conjunctiva, corneoscleral limbus, cornea). The OcS is vulnerable to infections which can be devastating leading to rapid loss of sight. Corneal scarring is a leading cause of preventable worldwide blindness. The mechanisms underpinning corneal fibrosis are complex but are linked to the Transforming growth factor- βs (TGF-β) and induction of toll-like receptors (TLRs). Decorin, a small leucine rich repeat protein, has been shown to attenuate the activity of TGF-β in various systemic fibrotic processes. In this study we examined the effect of decorin in suppressing TGF-β/TLR mediated pro-fibrotic activity in human corneal cells.
Primary cultures of human corneal fibroblasts (PHCF) were incubated with TGF-β1/2, TLR3/4, ± decorin and/or dexamethasone to investigate cellular migration using scratch assays, myofibroblastic (a-SMA) transformation using immunofluorescence and collagen production using Sirius-red assay. Whole human tearfilm decorin was quantified by ELISA.
TGF-β1/2 significantly increased PHCF migration (p<0.001), myofibroblast transformation (p<0.01) and collagen production (p<0.01), while TLR3 stimulation reduced collagen production (p<0.05). Decorin significantly inhibited TGF-β1/2 mediated cellular migration (p<0.001), collagen production and myofibroblastic (a-SMA) transformation. Dexamethasone antagonised the inhibitory effects of decorin in respect to collagen production and myofibroblast transformation, however this effect did not reach statistical significance. Decorin was detected in healthy human tears (1.62±0.18 ng/ml, mean n=3, range 2.57 - 0.54 ng/ml).
This study has shown the presence of decorin in human tears and is capable of inhibiting multiple TGF-β1/2 mediated pro-fibrotic processes. Decorin may have a protective anti-scarring role in physiological states and could provide a novel therapeutic modality to attenuate scarring during wound healing. Further work is required to characterise the interaction between glucocorticoid receptor agonists and the use of decorin.
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