Inhibition of matrix metalloproteinase activity in the chick sclera and its effect on myopia development.
OBJECTIVE
To investigate the contribution of matrix degradation in the two-layer avian sclera to the development of myopia.


METHODS
Tissue inhibitor of metalloproteinase-2 (TIMP-2) was used to inhibit chick scleral collagen degradation with (3)H-proline, a marker for this effect. Ex vivo scleral culture experiments confirmed TIMP-2 doses for in vivo experimentation. Ocular growth and refractive response to exogenous TIMP-2 (11.25, 2.25, and 0.45 picomoles, plus vehicle only) were monitored in 7-day-old chicks during the induction of myopia over 4 days with a translucent occluder. Collagen degradation was assessed, in whole sclera and in separated scleral layers by using the same paradigm (11.25 picomoles TIMP-2; vehicle only).


RESULTS
Approximately 60% of collagen degradation was inhibited with low (2 nM) doses of TIMP-2 in the ex vivo sclera. Degradative activity in the in vivo chick sclera increased significantly (46%) during myopia development, with all the altered activity confined to the fibrous layer. Addition of TIMP-2 significantly reduced (by 46%) this accelerated scleral collagen degradation, also by acting in the fibrous layer. TIMP-2 had no significant effect on (3)H-proline incorporated in the cartilaginous scleral layer and cornea. Despite inhibiting collagen degradation TIMP-2 had no significant effect on myopia development.


CONCLUSIONS
Increased collagen degradation is a feature of scleral remodeling in chick myopia development, but is confined to the fibrous scleral layer. Significant inhibition of this collagenolytic activity with TIMP-2 has little effect on refractive error development, suggesting that collagen degradation in the sclera contributes little to the development of myopia in the chick.
Department of Optometry and Vision Sciences, The University of Melbourne, Victoria, Australia.
Hsin-Hua
HH
Liu
Alex
A
Gentle
Andrew I
AI
Jobling
Neville A
NA
McBrien
D000818:Animals; D000831:Animals, Newborn; D001699:Biometry; D002645:Chickens; D003094:Collagen / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009216:Myopia / Q000503:physiopathology*; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D012590:Sclera / Q000201:enzymology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology
D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D006909:Hydroxyproline