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L. Yang; Valproic Acid Prevents Photoreceptor Cell Apoptosis in Retinitis Pigmentosa Mice by Increasing Bcl-2 Expression. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3691.
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© ARVO (1962-2015); The Authors (2016-present)
To observe the neuroprotective effect of valproic acid (VPA) on photoreceptor cells in retina pigmentosa mice and to study the mechanism of the protection.
48 neonatal C3H/HeJ mice were divided into two groups. One group received daily intraperitoneal (i.p.) injection of valproic acid (100mg/Kg·d), and the other received injection of same volume of saline. Mice were sacrificed on 7, 14, 21, and 28 days separately. Eyes were taken and retinas were sectioned. Histochemistry, TUNEL and immunofluorescence were conducted to analyze the retinal histology and apoptosis. Real-time PCR and western blot were used to measure the expression of Bcl-2 in retina.
The differentiation of inner and outer nuclear layers was finished on day 7 and photoreceptor cells began to loss gradually in both groups. There is no significant difference on the outer nuclear layer thickness and the count of photoreceptor cells between two groups on day 7. The outer nuclear layer thickness and the count of photoreceptor cells were higher in VPA group than in control group at other time point after day 7. In the control group photoreceptor cell apoptosis began on day 7 and peaked on day 14, but in VPA group the photoreceptor cell apoptosis began on day 14 and gradually decreased. The apoptotic cells count were much lower in VPA group than in control on any time point. There was significantly difference. The mRNA transcription level and the expression of Bcl-2 deceased slowly in both group, while it is higher in VPA group than in control.
Valproic acid may prevent photoreceptor cell apoptosis in the early stage of retina pigmentosa in mice, although it cannot fully stop the onset of retinal degeneration. The mechanism of apoptosis prevention maybe associated with the increasing of Bcl-2 expression.
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