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Yang Sun, Na Luo; Primary cilia signaling mediates intraocular pressure sensation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5655.
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Elevated intraocular pressure is a major risk-factor for glaucoma pathogenesis. The mechanisms for pressure mechanosensation are not well understood. Primary cilium is a membraneous organelle that may transduce extracellular signals. This study seeks to determine if primary cilia in the trabecular meshwork may be mechanosensors for pressure in the eye.
Confocal electron microscopy and immunofluorescence were used to examine the primary cilia in trabecular meshwork cells from humans, cows, pigs, rats and mice. Using trabeculectomy specimens from human patients and post-mortem eyes, we characterized primary cilia using IFT-88, acetylated alpha-tubulin, and gamma tubulin. In a flow-chamber model, we assessed the changes in TM cilia. Glaucoma-associated disease gene OCRL was examined in the TM cells.
Primary cilia were found in trabecular meshwork cells of all mammalian species examined. Changes in intraocular pressure resulted in cilia structural shortening as well as transcriptional activation of TNFa and TGFb. Inositol phosphatase OCRL was identified in primary cilia of TM cells. Nonfunctional OCRL affected cilia-mediated signal transduction, which was rescued by wild type OCRL.
Evolutionarily conserved in the trabecular meshwork, primary cilia can mediate mechanosensation in the eye.
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