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.
Liu
Hsin-Hua
HH
Department of Optometry and Vision Sciences, The University of Melbourne, Victoria, Australia.
Gentle
Alex
A
Jobling
Andrew I
AI
McBrien
Neville A
NA
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