title: Intraocular pressure lowering, change of antiapoptotic molecule expression, and neuroretinal changes by dorzolamide 2%/timolol 0.5% combination in a chronic ocular hypertension rat model.
abstract: The aim of this study was to examine intraocular pressure lowering, change of antiapoptotic molecules expression, and neuroretinal changes by a commercially available dorzolamide 2%/timolol 0.5% combination in a chronic ocular hypertension rat model. Chronic ocular hypertension was induced by three episcleral vein cauterizations. The expression of antiapoptotic molecules and the effect of dorzolamide 2%/timolol 0.5% combination in chronic ocular hypertensive retina were evaluated. Retinal ganglion cell (RGC) retrograde labeling and quantification with 4-di-10-ASP (DiA) and expression of glial fibrillary acidic protein (GFAP) were detected before and after the administration of dorzolamide 2%/timolol 0.5%. Treatment of ocular hypertensive eyes with dorzolamide 2%/timolol 0.5% significantly reduced, intraocular pressure when compared to the control eyes. Labeling of RGCs with DiA showed a significant decrease in RGC loss after the administration of dorzolamide 2%/timolol 0.5%. GFAP expression revealed a significant decrease in retinal damage after dorzolamide 2%/timolol 0.5% administration. However, dorzolamide 2%/timolol 0.5% did not affect Bcl-2 and Bcl-xL mRNA expression. In conclusion, dorzolamide 2%/timolol 0.5% may have neuroprotective potential in the animal model, which is not mediated by Bcl-2 or Bcl-xL. The mechanism of neuroprotection by dorzolamide 2%/timolol 0.5% in chronic glaucoma models requires further investigation.
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hae Y
authors.initials: HY
authors.lastname: Park
authors.forename: Na Y
authors.initials: NY
authors.lastname: Lee
authors.forename: Jie H
authors.initials: JH
authors.lastname: Kim
authors.forename: Chan K
authors.initials: CK
authors.lastname: Park
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004338:Drug Combinations; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*; D013999:Timolol / Q000008:administration & dosage*; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D004338:Drug Combinations; D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013449:Sulfonamides; D013876:Thiophenes; D051020:bcl-X Protein; D013999:Timolol; C062765:dorzolamide