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Hsin-Hua Liu, Alex Gentle, Megan S. Kenning, Neville A. McBrien; Replenishment of TIMP-2 Significantly Reduces Scleral Collagen Degradation and Axial Myopia in Tree Shrew. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6307.
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Increased degradation of scleral collagen, by the enzyme MMP-2, has been demonstrated during the development of experimental myopia in avian and mammalian models. The present study determined the endogenous regulation pattern of TIMP-2 in the tree shrew sclera during myopia development and investigated the capacity of exogenous TIMP-2 to inhibit both scleral collagen degradation and myopia development.
TIMP-2 expression during myopia development was assessed in two groups of tree shrews (n=7 each group), which underwent either 1 or 5 days of monocular form-deprivation to induce myopia. Scleral tissue was collected and assayed for TIMP-2 mRNA using real-time PCR. Two further groups of tree shrews were injected with [3H] proline, a collagen precursor, before undergoing 12 days of monocular form-deprivation with concurrent daily subconjunctival injections of either TIMP-2 (90µl, 125nM) or vehicle delivered to the occluded eye. Scleral tissue was collected and assayed for collagen degradation. Retinoscopy and A-scan ultrasound were used to monitor in vivo ocular biometry changes.
The development of myopia was associated with reduced TIMP-2 mRNA expression after 1 (-26±14%, p=0.12) and 5 (-47±14%, p=0.01) days of myopia induction. Replenishment of TIMP-2 significantly reduced myopia development by 60% (vehicle -11.9±0.5 D vs TIMP-2 -4.8±0.8 D, p<0.005), due to reduced vitreous chamber elongation (0.25±0.02 mm vs 0.14±0.01 mm, p=0.005). Collagen degradation in TIMP-2-treated sclerae was not significantly different to normal control eyes (+4±5%).
Myopia development in mammals is associated with reduced expression of TIMP-2, which contributes to increased, MMP-related, degradative activity in the sclera. Replenishment of TIMP-2 significantly reduces the rate of scleral collagen degradation and myopia development in mammals. This has clinical treatment applications for controlling axial myopia in human.
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