Abstract
Purpose :
Delayed re-epithelialization of the cornea, regardless of etiology, is linked to damage in the underlying basement membrane, Bowman’s membrane, and possibly stroma. The presence of damaged, disorganized collagen fibrils in these substrates hinders epithelial regeneration, while fully organized collagen enhances this process. Collagen Mimetic Peptides (CMPs), potential new topical therapeutics, reorganize damaged collagen and facilitate epithelial growth. This hypothesis was tested in vitro and in vivo.
Methods :
Type 1 collagen was damaged by MMP-1 in vitro, then exposed to CMPs (or to vehicle as a negative control) and subsequently seeded with epithelial cells. Comparison of epithelial cell growth was evaluated under the following conditions: undamaged collagen, damaged but untreated collagen, and damaged but CMP-treated collagen.
For in vivo studies, mouse eyes were wounded with a trephine and extended to 50% stromal depth manually using an Alger brush. Wounded eyes were treated with diluent or buffer as negative controls, with epidermal growth factor (EGF) as a positive control, or with one drop of a CMP solution. Digital fluorescein photography was performed at 16 and 24 hours after treatment. Central corneal histology was performed at 24 hours and stained using H&E.
Results :
CMPs were shown to reorganize damaged collagen three-fold better than control, in in vitro experiments. When used in vivo as treatment to damaged corneas, CMPs enhanced re-epithelialization with superior growth, superior reorganization, and superior adherence to Bowman’s membrane as compared to the negative controls. Total healing was observed in less than 24 hours in eyes treated with CMPs. Histology confirmed minimal to no inflammatory cells and total resolution of stromal edema in less than 24 hours.
Conclusions :
These results demonstrate that epithelial regeneration and healing is highly dependent on the state of repair of underlying collagen. Repairing the collagen matrix directly with a CMP results in very rapid and concomitant corneal healing. As such, we propose that clinical therapeutic CMPs can be used to treat the epithelial damage common to dry eye and other ocular surface diseases and have initiated work towards a Phase 2 Ora-CAE® Dry Eye Challenge trial.
This is a 2020 ARVO Annual Meeting abstract.