Sodium nitroprusside selectively induces apoptotic cell death in the outer retina of the rat

Abstract

Sodium nitroprusside (SNP), an NO donor, was studied for its effects on apoptosis in rat retinal neurons. TUNEL-positive cells were observed in the outer nuclear layer (ONL), but not in the inner retina after SNP treatment. Inner retinal neurons died by necrosis. No photoreceptor cells were found in the ONL after seven days. Immunoblotting confirmed that neurnal NO synthase expression increased up to 5 days (approximately 170% of control levels), and then declined by 7 days, suggesting that NO induces apoptosis in the ONL, and that inner retinal neurons die by necrosis due to glutamate from damaged photoreceptors.

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“…The present results strongly support the findings by Ju et al 15 that SNP selectively activates the apoptotic pathway in photoreceptors of the rat retina. NO is chemically generated from SNP 16 and it, rather than SNP itself, is the likely cause for the activation of the apoptotic pathway associated with photoreceptors.…”

“…One possibility is that it leads to an excessive build-up of cGMP in photoreceptors. 15 Pretreatment of rats with an NOS inhibitor is known to attenuate ischemia-induced photoreceptor death, 6 and cGMP levels are increased by SNP in photoreceptors, 28 supporting such a view. However, NO-induced photoreceptor apoptosis may involve other processes, because NO is a free radical that can therefore react with various intracellular constituents (e.g., superoxide) to produce the highly reactive substance peroxynitrite, which is known to cause cell damage.…”

“…Support for this idea comes from the finding that when SNP is injected into the aqueous chamber, photoreceptor apoptosis occurs. 15 It is likely that NO gas, generated from SNP, diffuses throughout the eye, causing apoptotic photoreceptor death (Fig. 2), whereas a chemical like SNP is unlikely to reach the retina from the aqueous chamber.…”

“…12,13 By virtue of its structure, docosahexaenoic acid is especially prone to lipid peroxidation, 14 and for this reason retinal photoreceptors are much more susceptible to NO when compared with other retinal cell-types. 15 For example, Ju et al, 15 injected the antihypotensive agent sodium nitroprusside (SNP) into the aqueous humor of the rat and particularly found the occurrence of photoreceptor death. SNP injected into the aqueous is unlikely to penetrate the vitreous.…”

“…This strongly supports the view that NO, which is spontaneously generated from SNP, 16 is produced in the aqueous chamber and can diffuse into the vitreous to ultimately cause death of photoreceptors. 15 Photoreceptor death can also be brought about experimentally in albino rats by excessive light, 11 injection of S-antigen to elicit experimental autoimmune uveitis (EAU), 17 or ischemia. 18,19 The cause in all cases appears to be the excessive production of free radicals.…”