Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol

Vidal, Lourdes; Díaz, F.; Villena, Alicia; Moreno, Mercedes; Campos, J. García; Vargas, I. Pérez de

doi:10.1016/j.brainresbull.2006.07.009

Cited by 32 publications

(24 citation statements)

References 57 publications

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“…It has been demonstrated in an experimental rat model of elevated intraocular pressure that high NO levels, synthesized by the NOS-1 and -2 isoforms, contribute to the progressive lesions of retinal ganglion cell axons; NO reduction after treatment with timolol, therefore, suggests a possible neuroprotective effect of timolol in neurons exposed to excessive amounts of NO. 42 Conversely, NOS-2 synthesis in glaucomatous optic neuropathy is not associated with a significant change in the expression of NOS-2 in the retina or optic nerve. 47 Accordingly, it can be proposed that timolol is devoid of vasodilating effect in the retinal and in posterior ciliary arteries, although a similar activity in other ocular compartments cannot be excluded.…”

Section: Discussionmentioning

confidence: 98%

“…It has been demonstrated that timolol displays a direct neuroprotective effect in experimental models of retinal injury and these protective effects are due in part to a mechanism independent of its action as an ocular hypotensive agent. 40 Some authors deny the neuroprotective effect of timolol; 41 nevertheless, recent studies support a potential neuroprotective effect of bblockers 40,42 although to a lesser extent than other molecules, 43 thus suggesting that the neuroprotective effect of timolol is possible, although in some way controversial.…”

Section: Discussionmentioning

confidence: 99%

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Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Izzotti

Saccà²,

Marco

et al. 2007

Eye

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Purpose A growing evidence in the scientific literature suggests that oxidative damage plays a pathogenic role in primary open-angle glaucoma. Therefore, it is of interest to test whether drugs effective against glaucoma display antioxidant activity. We test the hypothesis that the classic b-blocker therapy for glaucoma with timolol involves the activation of antioxidant protective mechanisms towards endothelial cells. Methods Oxidative stress was induced in cultured human endothelial cells by iron/ ascorbate with or without timolol pretreatment. Analysed parameters included cell viability (neutral red uptake and tetrazolium salt tests), lipid peroxidation (thiobarbituric reactive substances), and occurrence of molecular oxidative damage to DNA (8-hydroxy-2 0 -deoxyguanosine).Results Oxidative stress decreased 1.8-fold cell viability, increased 3.0-fold lipid peroxidation and 64-fold oxidative damage to DNA. In the presence of timolol, oxidative stress did not modify cell viability, whereas lipid peroxidation was increased 1.3-fold, and DNA oxidative damage 3.6-fold only.Conclusions The obtained results indicate that timolol exerts a direct antioxidant activity protecting human endothelial cells from oxidative stress. These cells employ mechanisms similar to those observed in the vascular endothelium. It is hypothesized that this antioxidant activity is involved in the therapeutic effect of this drug against glaucoma.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Izzotti

Saccà²,

Marco

et al. 2007

Eye

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“…Nesse estudo, houve decaimento gradual da expressão de nNOS, que retornou ao nível basal de expressão após 28 dias da lesão. Em outro modelo de lesão de células ganglionares da retina, onde foi induzido o aumento da pressão intraocular pela cauterização de vasos episclerais de ratos, também foi observado grande aumento da expressão de nNOS nas camadas mais internas da retina (VIDAL et al, 2006). Também pudemos observar tal diminuição da marcação de nNOS na GCL e NFL em retinas de animais com 21 dias de lesão do nervo óptico.…”

Section: Nossos Experimentos Deunclassified

“…Também pudemos observar tal diminuição da marcação de nNOS na GCL e NFL em retinas de animais com 21 dias de lesão do nervo óptico. Estes dados estão de acordo com dados recolhidos em outros estudos em que também foi demonstrado aumento da expressão da enzima nNOS como resposta a lesões axonais, como, por exemplo, em modelos de lesão neuropática que inclui a ligadura do nervo ciático (CIZKOVA et al, 2002;LEVY e ZOCHODNE, 1998 Não observamos expressão de iNOS em condições basais, assim como já foi relatado previamente (PANG et al, 2005;VIDAL et al, 2006). Devido a isso, escolhemos a imunoistoquímica para avaliar a expressão de iNOS nas retinas.…”

Section: Nossos Experimentos Deunclassified

“…Nos quadros com lesão do nervo óptico por 7 e por 21 dias, porém, é evidente o aparecimento de fibras positivas para a iNOS na retina interna. Em outro modelo, onde foi induzido o aumento da pressão intraocular, também foi observado grande aumento da expressão de iNOS nas camadas mais internas da retina (VIDAL et al, 2006). Porém, em um segundo trabalho utilizando modelo semelhante de aumento da pressão intraocular, não foi observada indução da expressão de iNOS na retinas e no nervo óptico (PANG et al, 2005) .…”

Section: Nossos Experimentos Deunclassified

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Receptores vanilóides TRPV1 na retina.

Leonelli¹,

Britto²

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Retinal Cell Death Induced by TRPV1 Activation Involves NMDA Signaling and Upregulation of Nitric Oxide Synthases

2013

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The activation of the transient receptor potential vanilloid type 1 channel (TRPV1) has been correlated with oxidative and nitrosative stress and cell death in the nervous system. Our previous results indicate that TRPV1 activation in the adult retina can lead to constitutive and inducible nitric oxide synthase-dependent protein nitration and apoptosis. In this report, we have investigated the potential effects of TRPV1 channel activation on nitric oxide synthase (NOS) expression and function, and the putative participation of ionotropic glutamate receptors in retinal TRPV1-induced protein nitration, lipid peroxidation, and DNA fragmentation. Intravitreal injections of the classical TRPV1 agonist capsaicin up-regulated the protein expression of the inducible and endothelial NOS isoforms. Using 4,5-diaminofluorescein diacetate for nitric oxide (NO) imaging, we found that capsaicin also increased the production of NO in retinal blood vessels. Processes and perikarya of TRPV1-expressing neurons in the inner nuclear layer of the retina were found in the vicinity of nNOS-positive neurons, but those two proteins did not colocalize. Retinal explants exposed to capsaicin presented high protein nitration, lipid peroxidation, and cell death, which were observed in the inner nuclear and plexiform layers and in ganglion cells. This effect was partially blocked by AP-5, a NMDA glutamate receptor antagonist, but not by CNQX, an AMPA/kainate receptor antagonist. These data support a potential role for TRPV1 channels in physiopathological retinal processes mediated by NO, which at least in part involve glutamate release.

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Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol

Cited by 32 publications

References 57 publications

Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Receptores vanilóides TRPV1 na retina.

Retinal Cell Death Induced by TRPV1 Activation Involves NMDA Signaling and Upregulation of Nitric Oxide Synthases

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