Purchase this article with an account.
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. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
This PDF is available to Subscribers Only