Neuroprotective actions of progesterone in an in vivo model of retinitis pigmentosa

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• 作者：V. Sá ; nchez-Vallejo^a ; S. Benlloch-Navarro^a ; R. Ló ; pez-Pedrajas^a ; F.J. Romero^b ; M. Miranda^a ; ^{mmiranda@uch.ceu.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Progesterone ; Retinitis pigmentosa ; Gliosis ; Glutamate ; Glutathione
• 刊名：Pharmacological Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：99
• 期：Complete
• 页码：276-288
• 全文大小：4027 K

文摘

Progesterone has been shown to have neuroprotective effects in experimental acute brain injury models, but little is known about the effects of steroid sex hormones in models of retinitis pigmentosa (RP). The aim of this study was to asses whether progesterone had a protective effect in one animal model of RP (the rd1 mice), and whether its action was due at least in part, to its ability to reduce free radical damage or to increase antioxidant defences.

Rd1 and wild type (wt) mice received an oral administration of 100 mg/kg body/weight of progesterone on alternate days starting at postnatal day 7 (PN7) and were sacrificed at different postnatal days.

Our results show that progesterone decreases cell death, as the number of TUNEL-positive cells were decreased in the ONL of the retina from treated rd1 mice. At PN15, treatment with progesterone increased values of ERG b-wave amplitude (m>p m>< 0,5) when compared with untreated mice. Progesterone also decreased the observed gliosis in RP, though this effect was transient.

Treatment with progesterone significantly reduced retinal glutamate concentrations at PN15 and PN17. To clarify the mechanism by which progesterone is able to decrease retinal glutamate concentration, we examined expression levels of glutamine synthase (GS). Our results showed a significant increase in GS in rd1 treated retinas at PN13.

Treatment with progesterone, significantly increase not only GSH but also oxidized glutathione retinal concentrations, probably because progesterone is able to partially increase glutamate cysteine ligase c subunit (GCLC) at PN15 and PN17 (m>pm> < 0,05).

In summary, our results demonstrate that oral administration of progesterone appears to act on multiple levels to delay photoreceptor death in this model of RP.