Abstract
Purpose :
Corneal opacity is a leading cause of worldwide blindness. The availability of drugs to treat established corneal scars or the prevention of scar formation following trauma, is limited. We have previously shown that Decorin, a naturally occurring antagonist of TGF-beta, creates a permissive microenvironment that enables healing with reduction of pro-fibrotic cascades. In this study, we examined the use of Decorin eye drops as an early stage intervention to reduce visually significant corneal scar formation in a corneal injury animal model.
Methods :
Decorin was delivered as a single 40µL drop onto the corneal surface of anaesthetised adult Sprague-Dawley rats and penetration into the cornea and aqueous humour (AqH) was assessed at 0, 30, 60 min by immunohistochemistry and ELISA, respectively. Eyedrop deliverable levels of Decorin were compared with those present endogenously in human AqH. An ex-vivo rat corneal-scarring alkali burn model was established by exposing the central cornea to filter paper saturated with 0.5M NaOH to varying time points (15, 30 and 60 s) followed by histological analysis of tissue for corneal scarring. The topical application of Decorin was evaluated.
Results :
Decorin penetrated the rat cornea into the anterior segment of the eye. While Decorin levels in corneal tissue increased over time, concentrations in the AqH decreased (10 min, 12600pg/mL (±3382pg/mL (SEM); n=3) to 60 min, 4600pg/mL (±3494pg/mL (SEM); n=3)). This level was comparable to physiological concentrations of Decorin in human AqH (1904pg/mL (± 360pg/mL (SEM); n=10). Topical Decorin is able to prevent corneal scar formation in our ex vivo rat corneal-alkali injury model compared to eyes that were not treated with Decorin.
Conclusions :
Topical application of Decorin is effective in reducing corneal scar formation during acute alkali injury and is likely to be therapeutically useful in the prevention of corneal scarring. Anterior-segment penetration of Decorin may afford a novel anti-fibrotic strategy for intraocular scarring processes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.