Ability of Dorzolamide Hydrochloride and Timolol Maleate to Target Mitochondria in Glaucoma Therapy

作者：Sacca Sergio Claudio^*; La Maestra Sebastiano; Micale Rosanna T; Larghero Patrizia; Travaini Giorgia; Baluce Barbara; Izzotti Alberto

来源：Archives of Ophthalmology, 2011, 129(1): 48-55.

DOI：10.1001/archophthalmol.2010.324

Objective: To test the ability of dorzolamide hydrochloride and timolol maleate to display antioxidant effects.
Methods: Antioxidant activity was tested in whole trabecular meshwork (TM) tissue as collected from corneal donors' biopsy specimens, young (third passage) and old (10th passage) human TM cells, and acellular systems composed of pure DNA and subcellular fractions containing or devoid of mitochondria. Oxidative stress was induced by hydrogen peroxide. Monitored end points included DNA fragmentation as evaluated by the halo test, oxidative DNA damage in terms of 8-hydroxy-2'-deoxyguanosine, and mitochondrial function as evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide test.
Results: The antioxidant effect of dorzolamide and timolol were observed on TM biopsy specimens and human TM cells exposed to hydrogen peroxide. As evaluated in cell subfractions, timolol displays antioxidant activity regardless of mitochondria presence. Conversely, the antioxidant activity of dorzolamide was maximized in the presence of mitochondria-containing subcellular fractions and in young human TM cells with functional mitochondria.
Conclusions: The antioxidant effect of timolol was direct. The antioxidant effect of dorzolamide involves mitochondria and is likely to be exerted mainly during the early glaucoma phases when the mitochondrial damage in the TM tissue still occurs at low levels.

• 出版日期2011-1