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Laura Claire Mairs, Michael D Conwell, Na Luo, Matthew J Turner, Yang Sun; Pressure-mediated primary cilia response in the trabecular meshwork. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5656.
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Increased intraocular pressure (IOP) is a risk factor that can lead to vision loss in patients with glaucoma. The mechanisms of mechanosensation of the trabecular meshwork are not entirely clear. Primary cilia have been shown to regulate pressure in the kidneys. The purpose of this study is to investigate the cellular mechanosensory mechanisms of trabecular meshwork (TM) cells and to determine if the cilia can play a sensory role in the TM.
A custom-made chamber system was designed to generate constant normal and elevated pressures in order to simulate anterior chamber IOP for bovine eyes and human TM cells. Immunofluorescence staining was performed to detect primary cilia changes in response to pressure. Quantitative real-time PCR (qRT-PCR) was also performed to determine downstream transcriptional activity.
In trabecular meshwork of bovine eyes under high pressure IOP for 6 hours, the lengths of primary cilia are significantly shorter in comparison to those with normal IOP (n=6, p value <0.05). Similarly shortened primary cilia were also found in cultured human TM cells that have undergone high chamber pressure treatment. Progressively shortened cilia were observed to be time- and pressure-dependent. qRT-PCR results showed a 2- to 8-fold increase in TNFα, Gli-1, and TGFβ mRNA levels in cells treated with elevated pressure. Disruption of cilia by shRNA of Rab8 blunted the mRNA response in HTM cells.
Primary cilia shortening and transcriptional changes in the TM cells support a role of cilia as mechanosensors in the eye.
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