Abstract
The cornea of the eye is at risk for injury through constant exposure to the extraocular environment. A highly collagenous structure, the cornea contains several different types distributed across multiple layers. The anterior-most layer contains non-keratinized epithelial cells that serve as a barrier to environmental, microbial, and other insults. Renewal and migration of basal epithelial cells from the limbus involve critical interactions between secreted basement membranes, composed primarily of type IV collagen, and underlying Bowman’s and stromal layers, which contain primarily type I collagen. This process is challenged in many diseases and conditions that insult the ocular surface and damage underlying collagen. We investigated the capacity of a collagen mimetic peptide (CMP), representing a fraction of a single strand of the damaged triple helix human type I collagen, to promote epithelial healing following an acute corneal wound. In vitro, the collagen mimetic peptide promoted the realignment of collagen damaged by enzymic digestion. In an in vivo mouse model, topical application of a CMP-containing formulation following a 360° lamellar keratectomy targeting the corneal epithelial layer accelerated wound closure during a 24 h period, compared to vehicle. We found that the CMP increased adherence of the basal epithelium to the underlying substrate and enhanced density of epithelial cells, while reducing variability in the regenerating layer. These results suggest that CMPs may represent a novel therapeutic to heal corneal tissue by repairing underlying collagen in conditions that damage the ocular surface.
Highlights
Collagen plays a well-known role as a biomechanical structural support for the integrity of most tissues and organs
We find that compared to a vehicle, collagen mimetic peptide (CMP) treatment accelerated the reestablishment of the epithelial layer and promoted structural adherence of the basal epithelium to the underlying anterior stroma surface
Our results show that CMPs have the potential as therapeutic agents to address conditions that challenge the cellular integrity of the cornea, albeit an effective treatment must demonstrate long-term benefits to vision without compromising corneal transparency
Summary
Collagen plays a well-known role as a biomechanical structural support for the integrity of most tissues and organs. Disruption of and damage to the collagen in these structures inhibit recovery of tissues that they support. In addition to providing biomechanical structural support, collagens serve a variety of additional functions. Specific cell-surface and intracellular receptors interact with collagens. Signaling by these receptors plays a key role in cellular adhesion, differentiation, growth, and other cellular activities, as well as the survival of cells both in vivo and in vitro (Vogel, 2001; Gelse et al, 2003). Collagens are involved in the entrapment, local storage, and delivery of growth factors
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