Corneal melting is an uncontrolled, excessive degradation of cellular and extracellular components of the cornea. This potential cause of corneal blindness is caused by excessive expression of zinc-dependent matrix metalloproteinases (MMPs) and has no satisfying cure as of now. Herein, we introduce a novel therapeutic hydrogel which can be made into a contact lens to slow down the progression of corneal melting by deactivating MMPs. The hydrogel backbone is comprised of poly(2-hydroxyetyl methacrylate) (pHEMA), a main material for commercial contact lenses, and dipicolylamine (DPA) which has high affinity and selectivity towards zinc ion. Due to the high affinity towards zinc ions, the DPA-conjugated pHEMA (pDPA-HEMA) hydrogel selectively removes zinc ions from a physiological buffer and deactivates MMP-1, MMP-2 and MMP-9 within 2 hours. pDPA-HEMA hydrogel also effectively prevents degradation of porcine corneas by collagenase A, a zinc-dependent protease, whereas the corneas completely degrades within 15 hours when incubated with pHEMA hydrogel. The presence of pDPA-HEMA hydrogel does not affect the viability of keratocytes and corneal epithelial cells. Unlike the conventional MMP inhibitors (MMPi), the pDPA-HEMA hydrogel minimizes the risk of serious non-specific side effects, and provides a method to slow down the progression of corneal melting and other related ocular diseases.
Keywords: contact lens; corneal melting; dipicolylamine; hydrogel; matrix metalloproteinases; zinc.