Matrix metalloproteinase 9-activatable peptide-conjugated hydrogel-based fluorogenic intraocular-lens sensor

The eye is an extension of the central nervous system (CNS) and contains aqueous humor (AH), which is a fluid rich in biomolecules secreted from intraocular tissues; thus, this organ allows for non-invasive visualization of early changes in CNS disorders. There is a growing interest in developing implantable devices, such as intraocular-lens (IOL), for specific medical uses, including intraocular monitoring. We describe a novel IOL-sensing system for detecting AH biomarkers via biocompatible enzyme-activatable fluorogenic hydrogel sensors. Matrix-metalloproteinase-9, a biomarker of degenerative CNS and eye disorders, was selected as a target. A peptide-probe-incorporated fluorogenic IOL (FIOL) was developed using diacrylamide-group-modified poly(ethyleneglycol) (PEGDAAm) biocompatible hydrogels, adjusting the hydrogel mesh size to allow selective penetration of the target while blocking non-targets, using label-free detection with semi-permanently implantable sensors, and demonstrating the clinical feasibility of FIOL through in vivo testing. This novel FIOL-based sensing system represents a promising approach for liquid biopsy of intraocular fluids. •The eye allows for early, non-invasive visualization of CNS disorders.•Implantable devices (intraocular-lens) are suitable for intraocular monitoring.•We detected AH biomarkers using enzyme-activatable fluorogenic hydrogel sensors.•FIOL was developed using PEGDAAm biocompatible hydrogels.•We proved the feasibility of FIOL-based sensing system for ocular liquid biopsy.