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Updated: Jul 7, 2025
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Published on: March 28, 2022
MicroRNA-152-3p and MicroRNA-196a-5p Are Downregulated When Müller Cells Are Promoted by Components of the Internal
Hung-Da Chou1,2,3,4, Shine-Gwo Shiah1,4, Lan-Hsin Chuang3,5
1Department of Life Sciences, National Central University, Taoyuan 32001, Taiwan.
Abstract:
Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research.
Insights
Internal limiting membrane components promote Müller cell migration. Specific microRNAs (miRNAs), including miR-152-3p and miR-196a-5p, regulate this process, offering potential therapeutic targets for macular hole healing.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Müller cells are crucial for macular hole closure, with their migration and proliferation influenced by the internal limiting membrane (ILM).
- The molecular mechanisms governing ILM-mediated Müller cell behavior are not fully understood.
Purpose of the Study:
- To investigate how internal limiting membrane (ILM) components affect the microRNA (miRNA) profile of Müller cells.
- To identify specific miRNAs involved in ILM-induced Müller cell migration and proliferation.
Main Methods:
- Rat Müller cells (rMC-1) were cultured on ILM component coatings (collagen IV, laminin, fibronectin).
- Cell migration was assessed using a cell-free area assay.
- MicroRNA (miRNA) expression was analyzed, and functional roles of candidate miRNAs were tested using mimics and inhibitors.
Main Results:
- ILM components significantly promoted Müller cell migration (p < 0.01).
- Several miRNAs were differentially regulated, with miR-194-3p upregulated and multiple others downregulated.
- miR-152-3p and miR-196a-5p were found to inhibit Müller cell migration and proliferation, effects reversible by inhibitors.
Conclusions:
- Internal limiting membrane (ILM) components modulate microRNA (miRNA) expression in Müller cells.
- miR-152-3p and miR-196a-5p play significant roles in regulating Müller cell migration and proliferation.
- These findings provide insights into the molecular basis of macular hole healing and suggest potential therapeutic targets.
