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N.N. Osborne, H. Allmeier, J.P. M. Wood; Lipid peroxidation and photoreceptor–induced apoptosis are blunted by metipranolol but no other ophthalmic ß–blocker . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3479.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To determine whether any of the currently used anti–glaucoma drugs have antioxidant properties and can blunt oxidative–stress induced apoptosis of photoreceptors. Methods: Lipid peroxidation in brain and retinal homogenates was stimulated by iron/ascorbate (Fe/As) or sodium nitroprusside (SNP). Lipid peroxidation was assessed by the formation of thiobarbituric acid reactive species (TBARS). SNP or Fe/As was injected into the vitreous humour and after three days the retinas processed histologically for breakdown of DNA by the TUNEL procedure and for caspase–3 and bcl–2 immunoreactivities. Extracts of retinas were also subjected to electrophoresis/blotting studies for analyses of poly (ADP–ribose) polymerase (PARP), caspase–3 and Bcl–2 protein content. Results: Of all anti–glaucoma drugs tested, only metipranolol and its active metabolite, desacetylmetipranolol, were found to significantly reduce Fe/As and SNP–induced lipid peroxidation. Metipranolol was only slightly less effective than Trolox (vitamin E analogue) at inhibiting SNP– induced lipid peroxidation (IC50 of 7 and 4µM for brain and retinal homogenates, respectively). Injection of Fe/As or SNP into the vitreous humour caused many photoreceptors to stain positively for TUNEL and both caspase–3 and Bcl–2 immunoreactivities were clearly upregulated in the photoreceptor layer of the retina, when compared with vehicle–treated animals. In addition, electrophoresis/blotting experiments showed that retinas from animals treated with SNP had an increase in the level of the active forms of caspase–2 and Bcl–2 proteins as well as an increased breakdown of PARP. Importantly, this effect of SNP was partially blunted when metipranolol was co–injected into the vitreous humour. Conclusions:Metipranolol exhibits remarkable anti–oxidant properties in blunting lipid peroxidation, in vitro. It also attenuates oxidant–induced stimulation of apoptosis to photoreceptors, in situ.
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