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Ankur Jain, Wei Zhu, Qihong Zhang, Markus H Kuehn, Abbot F Clark, Val Sheffield; Role of Primary Cilia in Trabecular Meshwork Cell Function. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3772. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Intraocular pressure (IOP) is mostly regulated by aqueous humor outflow through the trabecular meshwork (TM) and represents the only modifiable risk factor for glaucoma. Primary cilia are specialized organelles that play an important role in intraflagellar transport. The importance of primary cilia is observed in a group of disorders termed “ciliopathies”. The mechano-sensing role of primary cilia in TM function, IOP regulation and glaucoma remains largely unknown.
Number of cilia positive cells and ciliary lengths (immunochemically using anti-ARL13b antibody) were compared among cultured human primary normal (NTM) and glaucomatous TM (GTM) cell strains and tissues (n=3). Cilia were targeted by both chemical agents such as chloral hydrate and sodium pyrophosphate, and siRNA and CRISPR/Cas9 against intraflagellar proteins to study the effects on glaucoma-related insults including dexamethasone (DEX) and TGFβ2 signaling in TM.
Cultured GTM cell strains appear to have longer primary cilia as compared to NTM. Disrupting cilia results in affected DEX and TGFβ2 signaling (measured by SMAD and GRE-promoter reporter assays) as well as extracellular matrix synthesis in TM.
The differences among primary cilia on GTM vs NTM cell strains and involvement of primary cilia in DEX and TGFβ2 signaling suggest a prominent role of primary cilia in TM function and potential involvement in glaucoma pathophysiology.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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