miRNA Profiling of Human Optic Nerve Head Astrocytes Exposed to Cyclic Stretch

Purpose: Elevated intraocular pressure (IOP) is the primary risk factor for glaucoma, a leading cause of irreversible blindness involving the progressive loss of retinal ganglion cells (RGCs) and their axons. Elevated IOP induces biomechanical aberrations within ocular tissues – including the transmission of biomechanical stretch through the lamina cribrosa (LC) region of the optic nerve head (ONH), the site where RGC axon damage first occurs. LC cells and ONH astrocytes (ONHA), the primary cells of the LC, respond to stretch in a manner that promotes pathological extracellular matrix (ECM) remodeling and mechanical damage of RGCs within the ONH. A complex set of molecular mechanisms regulate ECM remodeling. Part of this regulation may involve microRNAs (miRNAs), small RNA molecules that can indirectly inhibit gene expression by binding messenger RNA. miRNA dysregulation may contribute to ECM remodeling during glaucoma progression. In this study, we examined miRNA expression profiles of ONHA exposed to cyclic stretch. Methods: Primary human normal ONHA cell strains (n=3) were exposed to 0-12% cyclic stretch for 24 hours. miRNA PCR arrays were used to determine expression changes in profibrotic and anti-fibrotic miRNAs. Results: We found that specific miRNAs were consistently dysregulated across three independent strains of ONHA. Statistical significance could not be detected, but these patterns may represent biologically meaningful changes. Conclusion: Stretch modulates miRNA expression in cultured human ONHA and may be responsible for ECM alterations at the LC. Dysregulated miRNAs may serve as novel targets or models for future therapeutics.