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 changes in proteinase activities. The latter include a 72 kDa matrix metalloproteinase (putatively MMP-2), other gelatin-binding MMPs, an acid pH MMP and a serine protease. Specifically, we have found that increases in scleral hydrational capacity parallel increases in collagen degrading activities. Gelatin zymography reveals that eyes with 7 days of retinal image degradation have elevated levels (1.4-fold) of gelatinolytic activities at 72 and 67 kDa M(r) in equatorial and posterior pole regions of the sclera while, after 14 days of treatment, increases are 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 extracts with an antibody to human MMP-2 reveals immunoreactive bands at 65, 30 and 25 kDa. Zymograms incubated under slightly acidic conditions reveal that, in enlarging eyes, MMP activities at 25 and 28 kDa M(r) are increased in scleral equator and posterior pole (1.6- and 4.5-fold respectively). A TIMP-like protein is also identified in sclera and cornea by Western blot analysis. Finally, retinal-image degradation also increases (approximately 2.6-fold) the activity of a 23.5 kDa serine proteinase in limbus, equator and posterior pole-sclera that is inhibited by aprotinin and soybean trypsin inhibitor. Taken together, these results indicate that eye growth induced by retinal-image degradation involves increases in the activities of multiple scleral proteinases that could modify the biomechanical properties of scleral structural components and contribute to tissue remodeling and growth.
Jones
B E
BE
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institute of Health, Bethesda, MD 20892, USA.
Thompson
E W
EW
Hodos
W
W
Waldbillig
R J
RJ
Chader
G J
GJ
D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism; D002645:Chickens; D003094:Collagen / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D005109:Extracellular Matrix / Q000201:enzymology*; D005123:Eye / Q000254:growth & development*; D018093:Gelatinases / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D009216:Myopia / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D012590:Sclera / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism
D003094:Collagen; D010450:Endopeptidases; D012697:Serine Endopeptidases; D018093:Gelatinases; D008666:Metalloendopeptidases