SCLERAL MATRIX METALLOPROTEINASES, SERINE PROTEINASE ACTIVITY AND HYDRATIONAL CAPACITY ARE INCREASED IN MYOPIA INDUCED BY RETINAL IMAGE DEGRADATION

In the avian model of myopia, retinal image degradation quickly leads to ocular enlargement. We now give evidence that, regionally specific changes in ocular size are correlated with both biomechanical indices of scleral remodeling, e.g. hydration capacity and with biochemical ch anges in proteinase activities. The latter include a 72 kDa matrix met alloproteinase (putatively MMP-2), other gelatin-binding MMPs, an acid pH MMP and a serine protease. Specifically, we have found that increa ses in scleral hydrational capacity parallel increases in collagen deg rading activities. Gelatin zymography reveals that eyes with 7 days of retinal image degradation have elevated levels (1.4-fold) of gelatino lytic activities at 72 and 67 kDa M(r) in equatorial and posterior pol e regions of the sclera while, after 14 days of treatment, increases a re no longer apparent. Lower M(r) zymographic activities at 50, 46 and 37 kDa M(r) are collectively increased in eyes treated for both 7 and 14 days (1.4- and 2.4-fold respectively) in the equator and posterior pole areas of enlarging eyes. Western blot analyses of scleral extrac ts with an antibody to human MMP-2 reveals immunoreactive bands at 65, 30 and 25 kDa. Zymograms incubated under slightly acidic conditions r eveal that, in enlarging eyes, MMP activities at 25 and 28 kDa M(r) ar e increased in scleral equator and posterior pole (1.6- and 4.5-fold r espectively). A TIMP-like protein is also identified in sclera and cor nea by Western blot analysis. Finally, retinal-image degradation also increases (similar to 2.6-fold) the activity of a 23.5 kDa serine prot einase in limbus, equator and posterior pole sclera that is inhibited by aprotinin and soybean trypsin inhibitor. Taken together, these resu lts indicate that eye growth induced by retinal-image degradation invo lves increases in the activities of multiple scleral proteinases that could modify the biomechanical properties of scleral structural compon ents and contribute to tissue remodeling and growth. (C) 1996 Academic Press Limited