Gelatinase B/matrix metalloproteinase-9 provokes cataract by cleaving lens betaB1 crystallin.
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 metalloproteinase-9 have been reported for cataract-associated disorders such as eye inflammation and diabetes. We demonstrate that incubation of lenses with gelatinase B leads immediately to cataract. In complete eye extracts, betaB1 crystallin was identified as the major gelatinase B substrate by combination of proteomics, mass spectrometry, and Edman degradation analysis. The cleavage of betaB1 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
Francis J
FJ
Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Martens
Erik
E
Proost
Paul
P
Starckx
Sofie
S
Van den Steen
Philippe E
PE
Van Damme
Jo
J
Opdenakker
Ghislain
G
D000818:Animals; D002386:Cataract / Q000201:enzymology* / Q000209:etiology*; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D003459:Crystallins / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry; D006801:Humans; D007178:Inbreeding; D007313:Insecta / Q000166:cytology; D007903:Lens Capsule, Crystalline / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000737:chemistry / Q000201:enzymology; D010446:Peptide Fragments / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D038206:beta-Crystallin B Chain
D002457:Cell Extracts; C491363:Crybb1 protein, mouse; D003459:Crystallins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D038206:beta-Crystallin B Chain; D020780:Matrix Metalloproteinase 9