Related Experiment Video
Updated: Aug 22, 2025
Inducement and Evaluation of a Murine Model of Experimental Myopia
Published on: January 22, 2019
miR-328-3p Affects Axial Length Via Multiple Routes and Anti-miR-328-3p Possesses a Potential to Control Myopia
Chung-Ling Liang1,2, Ku-Chung Chen3, Edward Hsi4
1Bright Eyes Clinic, Kaohsiung, Taiwan.
Purpose:
We previously reported miR-328-3p as a novel risk factor for myopia through a genetic association study of the PAX6 gene. In the present study, we first explored the effects of miR-328-3p on other myopia-related genes, and then tested whether anti-miR-328-3p may be used for myopia control.
Methods:
The luciferase report assay and transient transfection were used to confirm miR-328-3p target genes. The chromatin immunoprecipitation (ChIP) assay was used to investigate retinoic acid receptor on the miR-328-3p promoter. Mice and pigmented rabbits were induced to have myopia by the form deprivation method, and then anti-miR-328-3p oligonucleotide was topically instilled to the myopic eyes. The axial length was measured to assess the therapeutic effect of anti-miR-328-3p. A toxicity study using much higher doses was conducted to assess the safety and ocular irritation of anti-miR-328-3p.
Results:
The report assay and transfection of miR-328-3p mimic confirmed that miR-328-3p dose-dependently decreased both mRNA and protein expression of fibromodulin (FMOD) and collagen1A1 (COL1A1). We subsequently showed that FMOD promoted TGF-β1 expression, and overexpression of FMOD increased the phosphorylation levels of p38-MAPK and JNK. The ChIP study showed that retinoic acid binds to miR-328-3p promoter and up-regulates miR-328-3p expression. In myopic animal studies, anti-miR-328-3p was as effective as 1% atropine and had a dose-dependent effect on suppressing axial elongation. In the toxicity study, anti-miR-328-3p did not cause any unwanted effects in the eyes or other organs.
Conclusions:
Micro (mi)R-328-3p affects myopia development via multiple routes. anti-miR-328-3p possesses a potential as a novel therapy for myopia control.
Insights
MicroRNA-328-3p influences myopia development. Topical anti-microRNA-328-3p shows potential for myopia control, demonstrating efficacy and safety in animal models.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- MicroRNA-328-3p (miR-328-3p) was previously identified as a risk factor for myopia.
- The specific mechanisms by which miR-328-3p influences myopia development require further investigation.
Purpose of the Study:
- To investigate the effects of miR-328-3p on other myopia-related genes.
- To evaluate the therapeutic potential of anti-miR-328-3p for myopia control.
Main Methods:
- Luciferase reporter assays and transient transfections were used to identify miR-328-3p target genes.
- Chromatin immunoprecipitation (ChIP) assays examined retinoic acid receptor binding to the miR-328-3p promoter.
- Myopia was induced in mice and rabbits, followed by topical administration of anti-miR-328-3p to assess therapeutic effects on axial length and ocular safety.
Main Results:
- miR-328-3p was confirmed to dose-dependently decrease fibromodulin (FMOD) and collagen1A1 (COL1A1) expression.
- FMOD was found to promote TGF-β1 expression and increase p38-MAPK and JNK phosphorylation.
- Retinoic acid was shown to bind the miR-328-3p promoter, up-regulating its expression. Anti-miR-328-3p effectively suppressed axial elongation in myopic animal models, comparable to 1% atropine, with no observed toxicity.
Conclusions:
- MicroRNA-328-3p impacts myopia development through multiple pathways.
- Anti-miR-328-3p represents a promising novel therapeutic strategy for myopia control due to its efficacy and safety profile.
