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Updated: Jun 18, 2025
Scleral Cross-linking Using Riboflavin and Ultraviolet-A Radiation for Prevention of Axial Myopia in a Rabbit Model
Published on: April 3, 2016
The miR-15b-5p/miR-379-3p-FOXO axis regulates cell cycle and apoptosis in scleral remodeling during experimental
Ruixue Zhang1, Ying Wen2, Jinpeng Liu1
1Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.
Background:
Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia.
Methods:
The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling.
Results:
miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-β1 (TGF-β1), collagen type 1 (COL-1), and α-smooth muscle actin (α-SMA) were decreased, suggesting scleral remodeling occurred in myopia.
Conclusions:
miR-15b-5p/miR-379-3p can regulate the scleral cell cycle and apoptosis through the IGF1R/PTEN/FOXO signaling pathway, thereby promoting scleral remodeling in myopia progression.
Insights
MicroRNAs miR-15b-5p and miR-379-3p promote myopia progression by regulating scleral cell cycle and apoptosis via the IGF1R/PTEN/FOXO signaling pathway, driving scleral remodeling.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Myopia is a prevalent childhood eye disease.
- Scleral remodeling is implicated in myopia progression.
- The underlying molecular mechanisms remain unclear.
Purpose of the Study:
- Identify biomarkers for scleral remodeling in myopia.
- Elucidate the pathogenesis of myopia-associated scleral remodeling.
- Investigate the role of specific microRNAs in myopia.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) and Comparative Toxicogenomics Database (CTD) for miRNA-mRNA network analysis.
- Employed RT-qPCR, Western blot, and immunofluorescence to assess molecular changes.
- Conducted histological staining (H&E, Masson) and flow cytometry to evaluate cellular processes.
Main Results:
- miR-15b-5p/miR-379-3p were found to regulate the FOXO signaling pathway.
- Myopic sclera showed increased axial length, decreased thickness, and altered levels of key proteins (IGF1R, PTEN, FOXO3a, CDKN1B).
- Evidence of G1/S cell cycle arrest, enhanced apoptosis, and reduced fibrosis markers (TGF-β1, COL-1, α-SMA) in myopic sclera.
Conclusions:
- miR-15b-5p/miR-379-3p regulate scleral cell cycle and apoptosis.
- The IGF1R/PTEN/FOXO signaling pathway is a key mediator in myopia progression.
- These microRNAs promote scleral remodeling, contributing to myopia development.
