RESUMO
Ocriplasmin, a 249-amino acid recombinant C-terminal fragment of human plasmin, has the potential to degrade, within the eye, the protein scaffold that links the vitreous to the retina. This may be beneficial to the treatment of a number of important ophthalmic indications, such as symptomatic vitreomacular adhesion. We demonstrate here that ocriplasmin used at therapeutically-relevant concentrations is inactivated in porcine vitreous through autolytic degradation. Autolytic cleavage occurs at a limited number of sites, primarily K156-E157, K166-V167 and R177-V178, which, as predicted, contain a positively-charged arginine or lysine residue at the P1 position. Our data also suggest that autolytic degradation requires at least local or partial unfolding of the protein.