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Scleral Cross-linking Using Riboflavin and Ultraviolet-A Radiation for Prevention of Axial Myopia in a Rabbit Model
Published on: April 3, 2016
Mfn2 Regulates Scleral Remodeling in Myopia by Maintaining Endoplasmic Reticulum Homeostasis in Scleral Fibroblasts
Yiyan Wang1, Shuting Liu1, Qiong Huang1
1Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Purpose:
Endoplasmic reticulum (ER) stress participates in the development of various disorders by regulating tissue remodeling and apoptosis. This study aimed to explore the regulatory role of mitofusin 2 (Mfn2)-mediated ER stability in scleral remodeling in myopia.
Methods:
Myopia was induced in rats by form deprivation and hyperopic defocus. Scleral remodeling, ER stress, oxidative stress, and Mfn2 protein expression were examined in vivo. ER and mitochondrial ultrastructure were assessed by electron microscopy, and tissue apoptosis was evaluated. Primary rat scleral fibroblasts (SFs) were exposed to hypoxia to establish an in vitro myopia model, and Mfn2 expression in SFs was interfered by cell transfection. The extent of SFs transdifferentiation, extracellular-matrix remodeling, ER stress, mitochondrial damage, and cell apoptosis were assessed.
Results:
In this study, we discovered that tissue remodeling was accompanied by ER stress and oxidative stress in the sclera of myopic rats. Concomitantly, Mfn2 expression levels were significantly decreased, and the structures of the ER and mitochondria were damaged, along with tissue apoptosis. In vitro study showed that both hypoxia induction and MFN2 knockdown significantly increased hypoxia-inducible factor-1α expression in SFs. Mfn2 overexpression inhibited the transdifferentiation of hypoxia-induced SFs into myofibroblasts and upregulated the expression of collagen Iα1. Additionally, Mfn2 overexpression alleviated ER stress and mitochondrial damage in hypoxia-induced SFs, and reduced apoptosis of SFs.
Conclusions:
Our study revealed a critical role of Mfn2 in maintaining ER homeostasis in SFs, which conferred protective effects during scleral remodeling and provided a new therapeutic target for myopia.
Insights
Mitofusin 2 (Mfn2) plays a key role in maintaining endoplasmic reticulum (ER) stability. This study shows Mfn2 protects against scleral remodeling in myopia by reducing ER stress and apoptosis, offering a new therapeutic target.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Endoplasmic reticulum (ER) stress is implicated in tissue remodeling and apoptosis in various diseases.
- Scleral remodeling is a key factor in the development of myopia.
- Mitofusin 2 (Mfn2) is involved in ER and mitochondrial function.
Purpose of the Study:
- To investigate the role of Mfn2-mediated ER stability in scleral remodeling in myopia.
- To explore the therapeutic potential of Mfn2 in myopia.
Main Methods:
- Myopia was induced in rats using form deprivation and hyperopic defocus.
- In vivo and in vitro models were used to assess scleral remodeling, ER stress, oxidative stress, and Mfn2 expression.
- Primary rat scleral fibroblasts (SFs) were subjected to hypoxia, and Mfn2 expression was manipulated.
Main Results:
- Myopic rat sclera exhibited ER stress, oxidative stress, decreased Mfn2 expression, ER and mitochondrial damage, and apoptosis.
- Hypoxia and Mfn2 knockdown increased hypoxia-inducible factor-1α in SFs.
- Mfn2 overexpression inhibited SF transdifferentiation, reduced extracellular matrix remodeling, alleviated ER stress and mitochondrial damage, and decreased apoptosis.
Conclusions:
- Mfn2 is crucial for maintaining ER homeostasis in scleral fibroblasts.
- Mfn2 exerts protective effects against scleral remodeling in myopia.
- Mfn2 represents a potential therapeutic target for myopia treatment.
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