Matrix Metalloproteinase-14 as an Instigator of Fibrosis in Human Pterygium and Its Pharmacological Intervention

There exists a paucity of information on the pathogenesis of pterygium, a benign ocular tumor that scars the cornea and can lead to vision loss. The main recourse for pterygium is surgery; however, recurrence is observed. Matrix metalloproteinases (MMPs) are involved in the pathology of pterygium. The determination of the specific MMP involved among the 24 human enzymes has not been established due to challenges in MMP profiling. We used an affinity resin that binds specifically to the active forms of MMPs in the complex mixture of the cellular proteome. The proteomics analysis identified active MMP-14 and three related metalloproteinases, ADAM9, ADAM10, and ADAM17, in human pterygia. Inhibition of MMP-14 with the small-molecule inhibitor ( R )-ND-336 was assessed in cell migration and collagen contraction assays. ( R )-ND-336 attenuated human conjunctiva fibroblast migration and mitigated collagen contraction, both activities required for the formation of pterygium. ( R )-ND-336 holds the promise of a therapeutic recourse for pterygium as an orphan disease.