BMP-2 Is Involved in Scleral Remodeling in Myopia Development.

Honghui Li,Junwen Zeng,Jianmin Hu,Dongmei Cui,Lijun Huo,Feng Zhao,Xiangtian Zhou

doi:10.1371/journal.pone.0125219

Abstract

The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1). Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG) and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia.

Highlights

Myopia is a highly prevalent ocular disease worldwide[1,2,3,4]
Refraction and axial length had regressed at one week after lens removal in the recovery group, and there were no differences in refraction (p = 0.14) or axial length (p = 0.87) between the treated and control eyes after recovery
This study showed that bone morphogenetic protein-2 (BMP-2) was down-regulated in the sclera of lens-induced myopia guinea pig and that Bone morphogenetic proteins (BMPs)-2 promoted the synthesis of extracellular matrix (ECM) in human scleral fibroblasts (HSFs) in vitro

Summary

Introduction

The major structural change in myopia is an excessive increase in axial length[5,6] This ocular enlargement increases the risks of pathological damage such as macular degeneration, subretinal hemorrhage and retinal detachment, leading to irreversible vision loss and blindness[7,8]. During the development of myopia, scleral collagen accumulation decreases[11,12] and its degradation increases[13,14], and these changes result in scleral dry weight loss[15]. After these changes, scleral collagen fibril diameter decreases at the posterior pole of myopic eyes[9]. Changes in the scleral extracellular matrix during myopia development have been reported, the cellular and signaling factors that drive such changes have not been determined

Methods

Results

Conclusion