Abstract
Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-β dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-β dependent cell differentiation.
Highlights
IntroductionHealthy cornea is a transparent avascular tissue and is formed by three cellular layers (epithelium, stroma, endothelium) distinctively separated by acellular membranes (Bowman’s and Descemet’s membrane)
Healthy cornea is a transparent avascular tissue and is formed by three cellular layers distinctively separated by acellular membranes (Bowman’s and Descemet’s membrane)
Tissue samples from human and murine cornea, conjunctiva, lacrimal gland, efferent tear duct, eyelid, lung, liver and stomach as well as three different human epithelial cell lines, i.e. a human corneal epithelial cell line (HCE), a human conjunctival epithelial cell line (HCjE) and a human meibomian gland epithelial cell line (HMGEC) were tested positive for GSN mRNA (Fig. 1A,B). ß-actin served as loading control for all samples
Summary
Healthy cornea is a transparent avascular tissue and is formed by three cellular layers (epithelium, stroma, endothelium) distinctively separated by acellular membranes (Bowman’s and Descemet’s membrane). The most superficial cell layer to which the tear film attaches is the corneal epithelium Corneal surface diseases such as injuries, dry eye disease (DED), systemic inflammatory disorders with ocular involvement (e.g. Stevens-Johnson syndrome, ocular cicatricial pemphigoid), chemical or thermal burns, and in some cases medical or surgical interventions, may be accompanied by impaired or delayed re-epithelialization of the corneal epithelium and can result in deterioration of visual acuity[1]. Such impaired wound healing can occur in other epithelia, for example various mucosal and dermal tissues, and is observed with increasing frequency, especially in the elderly and in patients suffering from chronic conditions like diabetes mellitus or metabolic syndrome[2]. It is of special importance for phagocytosis and the proper function of thrombocytes[20,21]
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