Gelatinase B/matrix metalloproteinase‐9 provokes cataract by cleaving lens βB1 crystallin

Abstract

Cataract is a common cause of blindness and results from destruction of the microarchitecture of the lens. It is observed in many genetic syndromes, infections, inflammatory diseases and during aging. Fluctuations in lens density and light scattering by altered refraction index form the physical basis for this process, but the pathogenesis is poorly understood. Increased levels of gelatinase B/matrix metalloprotein- ase-9 have been reported for cataract-associated disor¬ders such as eye inflammation and diabetes. We dem¬onstrate that incubation of lenses with gelatinase B leads immediately to cataract. In complete eye extracts, βB1 crystallin was identified as the major gelatinase B substrate by combination of proteomics, mass spec¬trometry, and Edman degradation analysis. The cleav¬age of βB1 crystallin was also observed in vivo after endogenous gelatinase B-induction by the chemokine granulocyte chemotactic protein-2 in wild-type mice but not in gelatinase B^−/− mice.—Descamps, F. J., Mar¬tens, E., Proost, P., Starckx, S., Van den Steen, P. E., Van Damme, J., Opdenakker, G. Gelatinase B/matrix metalloproteinase-9 provokes cataract by cleaving lens βB1 crystallin. FASEB J. 19, 29-35 (2004)