Abstract
Purpose:
Corneal opacity is a leading cause of blindness that is often a result of corneal scarring and vascularisation from infectious diseases, inflammation and corneal trauma. Amniotic membrane overlay is used to modify healing processes to reduce scarring of optically clear tissues by releasing anti-fibrotic/anti-inflammatory factors and mobilization of epithelial cells. Reproducibility and repeatability of this effect is limited due to inter and intra amnion biological variability demanding the development of a synthetic and consistent bio-similar alternative. We have developed a gel dressing that can be applied topically to the surface of the eye and releases the anti-scarring agent, decorin, in a sustained manner to the cornea.
Methods:
Gel dressings were produced by heating the hydrocolloid to melting point and, by controlled temperature processing; the temperature was reduced to form a gel. In vitro decorin release studies from the gel dressing were carried out using an ELISA quantification assay. The anti-fibrotic bioactivity of the decorin released was determined using primary human corneal fibroblast monolayer cultures (hCFs) that were stimulated to produce excess collagen using TGF-β1. Transparency and setting times of the gels were also tested on enucleated pig’s eyes.
Results:
The gels containing the anti-scarring molecule released a sustained dose of decorin over 4h. When overlain on hCFs monolayer cultures, the gels did not compromise cell viability or metabolic activity when compared with hCFs cultures without the gel. Collagen production was significantly reduced (p<0.05) over a 12-day period in hCFs cultures with the decorin gel when compared with gels containing no decorin. Rheological analysis of the gel on pig eyes showed that the gel increased in stiffness and quickly formed a transparent layer when spread on top of the ocular tear film.
Conclusions:
We have successfully developed a gel ‘eye drop’ therapy with potential to be used as a topical treatment to prevent corneal scarring. The properties allow a sustained, effective release of decorin over 4h after application with the added benefit of providing a protective ocular surface dressing facilitating healing without reducing ocular transparency.