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Inhibition of matrix metalloproteinase activity in the chick sclera and its effect on myopia development.

Liu HH, Gentle A, Jobling AI, McBrien NA

Optometry and Vision Sciences, The University of Melbourne, Parkville, Australia.

Purpose: To investigate the contribution of matrix degradation in the two-layer avian sclera to the process of myopia development. Methods: Tissue inhibitor of metalloproteinase-2 (TIMP-2) was used to inhibit chick scleral collagen degradation with 3H 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 pmoles, plus vehicle only) was 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 separated scleral layers using the same paradigm (11.25 pmoles TIMP-2; vehicle only). Results: Approximately 60% of collagen degradation could be inhibited with low (2 nM) nanomolar doses of TIMP-2 to the ex vivo sclera. Degradative activity in the in vivo chick sclera increased significantly (46%) during myopia development with all of this altered activity confined to the fibrous layer. Addition of TIMP-2 significantly reduced (by 46%) this accelerated scleral collagen degradation, also through actions in the fibrous layer. TIMP-2 had no significant effect on 3H 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 remodelling in chick myopia development, but is confined to the fibrous scleral layer. However, 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 chick.

Published 4 February 2010 in Invest Ophthalmol Vis Sci.
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