Abstract
Abstract: :
Purpose: It has been reported that light–induced oxidative stress is one cause of atrophic macular degeneration, a condition associated with aging. Carteolol hydrochloride (the active ingredient in Mikelan® eye drops), a ß–adrenoceptor antagonist used in the treatment of glaucoma, has antioxidant activity and may be effective in the treatment of atrophic macular degeneration. For this reason, the rat model of light–induced retinal damage, which mimics the pathogenesis of atrophic macular degeneration, was used to evaluate the effectiveness of Mikelan® eye drops. In addition, a comparison of this drug in efficacy was made using drugs of the same class, timolol maleate, which have been reported to be effective in the similar experimental models. Methods: Brown–Norway male rats maintained in a dark environment of less than 10 Lux were given ophthalmic administration of saline (control), Mikelan® eye drops (carteolol hydrochloride 2% formulation) or Timoptol® eye drops (timolol maleate 0.5% formulation) twice a day everyday for two weeks. After the administration, the animals were exposed to approximately 8000 Lux of visible light (fluorescent light) for a given period of time and then evaluated by ERG function measurements, as well as a pathologic examination of the retinal tissue [measurement of 8–OHdG generation and thickness of the outer nuclear layer (ONL)]. Results: Exposure to visible light in the dark–adapted rats in the saline group resulted in lower ERG values (a–wave and b–wave) and thinning of the retinal ONL. Animals in this group also showed an increase in the 8–OhdG, an index of oxidative damage to DNA, in the ONL after exposure to light. The extent of the retinal damage in the Mikelan® eye drops was significantly less than the saline administered group. The efficacy of Timoptol® eye drops was slight. Conclusions: Mikelan® eye drops protected the retina from light–induced injury and may have some utility in preventing atrophic macular degeneration. We speculate that the antioxidant effects of carteolol hydrochloride are involved in the expression of this effect.
Keywords: retina • drug toxicity/drug effects • radiation damage: light/UV