MiR-328-3p Affects Axial Length Via Multiple Routes and Anti-miR-328-3p Possesses a Potential to Control Myopia Progression

Chung Ling Liang, Ku Chung Chen, Edward Hsi, Jui Yu Lin, Chien Yuan Chen, Jung Kai Tseng, Suh Hang H. Juo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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. antimiR-328-3p possesses a potential as a novel therapy for myopia control.

Original languageEnglish
Article number11
JournalInvestigative Ophthalmology and Visual Science
Volume63
Issue number12
DOIs
Publication statusPublished - Nov 2022

Keywords

  • axial length
  • eye drops
  • microRNA-328
  • myopia
  • oligonucleotide

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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