Effects of timolol on MYOC, OPTN, and WDR36 RNA levels.
OBJECTIVE
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.


CONCLUSIONS
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.
Rozsa
Frank W
FW
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Scott
Kathleen
K
Pawar
Hemant
H
Moroi
Sayoko
S
Richards
Julia E
JE
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002648:Child; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004338:Drug Combinations; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D013999:Timolol / Q000494:pharmacology*; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism; D035582:Transcription Factor TFIIIA / Q000096:biosynthesis / Q000235:genetics*; D000099179:Myocilin
D000319:Adrenergic beta-Antagonists; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D003907:Dexamethasone; D004338:Drug Combinations; D005136:Eye Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D012313:RNA; D038621:Regulatory Sequences, Ribonucleic Acid; D013999:Timolol; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human; C502341:WDR36 protein, human