Effect of MT3 on Retinal and Choroidal TGF-β2 and HAS2 Expressions in Form Deprivation Myopia of Guinea Pig

Tao Li,Bo Jiang,Bing Li,Xiaodong Zhou

doi:10.1155/2017/5028019

Abstract

Purpose To confirm its dose-dependent effect on form deprivation myopia and evaluate the effect of MT3 at different tissue concentrations on changes in mRNA and protein expression for TGF-β2 and HAS2. Methods MT3 was intravitreally injected into deprived eyes at two-day intervals. Refraction was measured by streak retinoscopy after cycloplegia. The axial dimensions were measured by A-scan ultrasound. The quantitative RT-PCR and Western blot were used to detect the changes of TGF-β2 and HAS2 expressions in the retina and choroid of guinea pigs. Results MT3 treatment produced a significant dose-dependent reduction in relative myopia compared to FD group (both p < 0.001). There were statistically significant increases in retinal and choroidal mRNA levels for both TGF-β2 and HAS2 after injections of 10 μM of MT3, when compared to the FD group. There were no significant differences in retinal and choroidal TGF-β2 protein expression levels between the MT3 treatment groups and FD group (all p > 0.05). The injections of 10 μM of MT3 caused a marked decrease in retinal HAS2 protein expression level, when compared to the FD group (p = 0.001). Conclusion MT3 can inhibit form deprivation myopia, and MT3 treatment can result in changes of retinal and choroidal TGF-β2 and HAS2 mRNA and protein expressions.

Highlights

Myopia is an increasingly widespread condition around the world, in Eastern Asia [1,2,3]
Since Transforming growth factor (TGF)-β2 and Hyaluronan synthase 2 (HAS2) may be involved in the development of form deprivation myopia [18,19,20, 25], in a second step, we studied the effect of MT3 at different tissue concentrations on changes in mRNA and protein expression for TGF-β2 and HAS2
The present study demonstrates that the selective M4 muscarinic receptor antagonist MT3 is effective in significantly inhibiting form deprivation myopia (FDM) in the guinea pigs in a dose-dependent manner

Summary

Introduction

Myopia is an increasingly widespread condition around the world, in Eastern Asia [1,2,3]. High myopia is characterized by a progressive elongation of the eye ball and scleral thinning. Those with high myopia are at a high risk of subsequent retinochoroidal pathologies and blindness [4, 5]. This emphasizes the importance of controlling the myopic development by slowing axial elongation. The selectivity for M1 receptors of pirenzepine is only fourfold higher than that for M4 receptors [11], so it is clear that pirenzepine is binding to M4 receptors These findings highlight the problem of identifying which specific muscarinic receptors are responsible for myopia inhibition. It is reported that MT3 effectively inhibits the development of FDM in animal models [14,15,16]

Methods

Results

Conclusion