Dynamic expression changes of Smad3 and type Ⅰ collagen in sclera of progressive myopia in guinea pigs

Authors: Jiang Bo,  Wu Zhangyou,  Zhu Zicheng,  Hu Wei,  Zhan Xin

DOI: 10.3760/cma.j.issn.2095-0160.2017.06.003
Published 2017-06-10
Cite as Chin J Exp Ophthalmol, 2017,35(06): 491-497.

Abstract

Background

Sclera remodeling process in axial elongation is one of the main pathological mechanisms of axial myopia progression.Studies confirmed that transforming growth factor-β1 (TGF-β1) participates in the sclera remodeling process, and Smad3 is one of TGF-β1 downstream signal gene transcriptive factors, so to explore its role in sclera remodeling process of myopic eyes is of great significance for pathogenesis and prevention research of myopia.

Objective

This study was to investigate the expressions of type Ⅰ collagen and Smad3, a TGF-β1 downstream target, in sclera of form deprivation myopic (FDM) eyes and explore the impact of TGF-β1-Smad3-type I collagen signaling pathway on collagen remodeling in myopic sclera.

Methods

Seventy-five 1-week-old guinea pigs were randomly divided into normal control group (25 guinea pigs) and FDM group (50 guinea pigs). Monocular FDM was induced by occluding the left eyes of guinea pigs in FDM group with translucent latex balloons for 2, 4, 6 weeks, respectively, and consecutive occluding for 4 weeks followed by uncovering for 1 week (4/-1 weeks). The refractive power was detected by retinoscopy and axial length was measured with A-type ultrasound.Immunohistochemistry and reverse transcription-PCR were employed to detect the dynamic expressions of type Ⅰ collagen and Smad3 protein ad mRNA in the sclera of guinea pigs with emmetropia and experimental myopia, and the relationship between collagen Ⅰ and Smad3 levels was analyzed.

Results

The refraction was hypermetropic in both normal control group and FDM group before occluding of eyes (P>0.05), and the hypermetropic power was gradually reduced over time in the normal control group.In the FDM group, the refractive power was gradually changed from (+ 2.09 ± 0.31)D before occluding to (-1.23±0.69), (-4.17±0.59), (-7.07±0.56) and (-4.30±0.58)D, and the axial length was increased from (5.93±0.39)mm to (6.62±0.36), (7.30±0.34), (7.99±0.32), and (7.21±0.36)mm at weeks 2, 4, 6, and 4/-1 after occluding, respectively, indicating significant differences in refractive power and axial length over time in the FDM group from normal control group and self-control group (all at P<0.05). The expressions of Smad3 and type Ⅰ collagen protein and mRNA in the sclera of the FDM group was significantly lower than those of the control group and self-control group in various time points (all at P<0.05). The positive correlation were found in the expression of Smad3 on the myopic sclera with that of type Ⅰ collagen in both protein and mRNA levels (protein: r=0.993, P<0.05; mRNA: r=0.954, P<0.05).

Conclusions

The myopic power and ocular axis increase dependent upon occluding time, and the expressions of Smad3 and type Ⅰ collagen in the sclera are correspondingly weakened in FDM eyes.A consistent expression trend is found between Smad3 and type Ⅰ collage, suggesting Smad3 and type Ⅰ collagen participate in the regulation of sclera remodeling in myopia by TGF-β1-Smad3-CollagenⅠsignaling pathway.

Key words:

Form-deprivation; Myopia; Sclera/metabolism; Disease progression; TGF-β1-Smad3-Collagen Ⅰ signaling pathway; Disease models, animal; Guinea pigs

Contributor Information

Jiang Bo
Department of Ophthalmology, Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China
Wu Zhangyou
Zhu Zicheng
Hu Wei
Zhan Xin
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Updated: September 4, 2019 — 1:10 pm