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Xin Wang, Gezhi Xu, Department of Ophthalmology and Vision Sciences, Eye and ENT Hospital,Fudan University; Gene expression changes under cyclic mechanical stretching in rat retinal glial (Müller) cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):297.
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© ARVO (1962-2015); The Authors (2016-present)
To identify patterns of gene expression changes induced by cyclic mechanical stretching in Müller cells.
Rat Müller cells were seeded onto flexible bottom culture plates and subjected to a cyclic stretching regimen of 15% equibiaxial stretching for 1 and 24 h. RNA was extracted and amplified, labeled, and hybridized to rat genome microarrays. The expression profiles were analyzed using GeneSpring software, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis was used to find the association with biological functions. The selected genes of interest were further validated by RT-qPCR.
An analysis of microarray data showed that at 1 and 24 h, the expression of 532 and 991 genes in the Müller cells significantly (T-test, p < 0.05) differed between the mechanically stretched and the unstretched groups. At 1 h, 52 genes, which are involved in response to stimuli, developmental processes, transcription regulator activity, and regulation of biological processes, showed at least a twofold change in expression. At 24 h, 63 genes, which are involved in developmental processes, anatomical structure formation, and extracellular regions, showed at least a twofold change in expression. KEGG canonical pathway analysis showed significant changes in MAPK signaling, ErbB signaling, TGF-beta signaling, and Wnt signaling at both time points.
Cyclic mechanical strain induces extensive changes in the gene expression in Müller cells through multiple molecular pathways. These results indicate the complex mechanoresponsive nature of Müller cells, and they may help in excluding possible novel molecular mechanisms that would account for many retinal diseases in which the retina is often subjected to mechanical forces, such as degenerative axial myopia and proliferative vitreoretinopathy.
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