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Effects of Timolol on MYOC, OPTN, and WDR36 RNA Levels
Frank W. Rozsa, PhD;
Kathleen Scott, BS;
Hemant Pawar, PhD;
Sayoko Moroi, MD, PhD;
Julia E. Richards, PhD
Arch Ophthalmol. 2008;126(1):86-93.
Objectives To evaluate if timolol affects expression of 3 open-angle glaucoma genes and to study its ability to modulate dexamethasone-induced up-regulation of MYOC.
Methods We used quantitative polymerase chain reaction assay of glaucoma gene transcript levels from human trabecular meshwork (HTM) cultures exposed to 3 different doses of timolol. Three HTM cell cultures were grown with or without 1 of 3 timolol doses in the presence or absence of dexamethasone.
Results All 3 concentrations of timolol reduced MYOC RNA levels in 1 HTM culture compared with an untreated control and showed negligible effects in the other 2 cultures. Timolol had no effect on dexamethasone-induced MYOC transcript levels in any of the 3 cultures. Timolol, dexamethasone, and dexamethasone plus timolol had a negligible effect on OPTN and WDR36 RNA levels.
Conclusions Timolol can reduce MYOC RNA levels in HTM cultures from some individuals. Timolol does not alter OPTN or WDR36 levels or ameliorate MYOC induction by dexamethasone in vitro.
Clinical Relevance It remains to be determined whether timolol could reduce production of misfolded myocilin protein by HTM cells in individuals with MYOC missense mutations. A broader survey of interindividual variation in response to timolol as well as mechanistic studies are still needed before potential therapeutic implications can be explored.
Author Affiliations: Departments of Ophthalmology and Visual Sciences (Drs Rozsa, Pawar, Moroi, and Richards and Ms Scott) and Epidemiology (Dr Richards), University of Michigan, Ann Arbor.
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