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Lin Cong, Jinling Zhang, Shu Ho Fu, Yu Zhang, Yuyan Zhang; Effects of Atorvastatin on Aqueous Humor Outflow and Porcine Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3004.
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© ARVO (1962-2015); The Authors (2016-present)
Increase in resistance to aqueous humor outflow through the trabecular meshwork (TM), which causes elevated intraocular pressure (IOP), is an important involved factor in primary open-angle glaucoma (POAG). However, there’s still no effective therapy for POAG against pathogenesis at present. Statin use was previously reported to be beneficial for POAG. We hypothesize that atorvastatin could affect aqueous humor outflow facility and TM cells.
Changes of aqueous humor outflow facility in porcine eyes were evaluated in a constant pressure whole-eye ex vivo perfusion system. Cultured primary TM cells were used to evaluate the biological effects of atorvastatin. Cellular distributions of cytoskeleton and adhesion proteins were detected by immunofluorescent staining. Quantitative changes of adhesion proteins were studied by RT-PCR and western blot. The potential toxicity of atorvastatin on TM cells was tested by viability assay.
Perfusion of enucleated porcine eyes with 50 to 200 μM atorvastatin for 2 hours caused significant increase in aqueous humor outflow facility (P<0.05, n=6) without washout effect. Atorvastatin affected TM cell shape and distribution of cytoskeleton in a dose-dependent manner. The drug also decreased the expression of adhesion proteins on both mRNA and protein levels. Concentration of atorvastatin below 100 μM showed no detectable toxicity on TM cells. At concentrations up to 100 μM, the atorvastatin induced effects were reversible after removal of the compound.
The study demonstrates that atorvastatin increases aqueous humor outflow efficaciously. The exact mechanism of action of this drug effect is not known, may be a result of its action on TM cells shape, cytoskeleton and cell junctions. These findings further support statins as potential therapeutic agents for lowering intraocular pressure in patients with primary open-angle glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
(A) Baseline outflow facility values were not significantly different among all groups. (B) Compared with control group, 50, 100 and 200 μM atorvastatin increased outflow facility significantly, while 17 μM atorvastatin did not show the same effect. *P<0.05.
Atorvastatin (10-200 μM) induces morphologic changes in TM cells.
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