Collagen Mimetic Peptides Promote Adherence and Migration of ARPE-19 Cells While Reducing Inflammatory and Oxidative Stress.

ABSTRACT

Epithelial cells of multiple types produce and interact with the extracellular matrix to maintain structural integrity and promote healthy function within diverse endogenous tissues. Collagen is a critical component of the matrix, and challenges to collagen's stability in aging, disease, and injury influence survival of adherent epithelial cells. The retinal pigment epithelium (RPE) is important for maintaining proper function of the light-sensitive photoreceptors in the neural retina, in part through synergy with the collagen-rich Bruch's membrane that promotes RPE adherence. Degradation of Bruch's is associated with RPE degeneration, which is implicated early in age-related macular degeneration, a leading cause of irreversible vision loss worldwide. Collagen mimetic peptides (CMPs) effectively repair damage to collagen helices, which are present in all collagens. Our previous work indicates that in doing so, CMPs promote survival and integrity of affected cells and tissues in models of ocular injury and disease, including wounding of corneal epithelial cells. Here, we show that CMPs increase adherence and migration of the ARPE-19 line of human RPE cells challenged by digestion of their collagen substrate. Application of CMPs also reduced both ARPE-19 secretion of pro-inflammatory cytokines (interleukins 6 and 8) and production of reactive oxygen species. Taken together, these results suggest that repairing collagen damaged by aging or other pathogenic processes in the posterior eye could improve RPE adherence and survival and, in doing so, reduce the inflammatory and oxidative stress that perpetuates the cycle of destruction at the root of age-related diseases of the outer retina.