Abstract:
PURPOSE:To determine the effect of the nitric oxide donor sodium nitroprusside (SNP) on rat retinas and to see whether detrimental changes could be attenuated by known antiglaucoma drugs. METHODS:SNP was injected into the rat eye and retinas were analyzed by the terminal-deoxynucleotidyl transferase dUTP-linked nick end labeling (TUNEL) procedure and by immunohistochemistry. In some instances, retinal homogenates were analyzed by immunoblot for proteins associated with either photoreceptors or with cell death. Analysis of lipid peroxidation in retinal homogenates was by the thiobarbituric acid reactive species (TBARS) formation METHOD: RESULTS:SNP caused an increase in the number of retinal photoreceptors labeled for DNA breakdown by the TUNEL procedure and for caspase-3 and Bcl-2. After intravitreal injection of SNP, breakdown of poly(ADP-ribose) polymerase and an increase in the level of active forms of caspase-3 and Bcl-2 were detected. Furthermore, photoreceptor-specific rhodopsin kinase was reduced. SNP also stimulated formation of TBARS in retinal homogenates, occurring to a greater extent in retinas from young Royal College of Surgeons rats lacking photoreceptor degeneration. This supports the view that the photoreceptors are the prime target for SNP. Significantly, of several antiglaucoma drugs tested only metipranolol and its active metabolite, desacetylmetipranolol, blunted the SNP-induced retinal changes. CONCLUSIONS:Of all antiglaucoma drugs tested, only metipranolol was able to attenuate SNP-induced lipid peroxidation and activation of apoptosis in photoreceptors. Because oxidative injury has been implicated in the pathogenesis of certain ocular diseases, these findings could prove to be of clinical significance.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Osborne NN,Wood JPdoi
10.1167/iovs.04-0147keywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
3787-95issue
10eissn
0146-0404issn
1552-5783pii
45/10/3787journal_volume
45pub_type
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