Abstract
Purpose: :
To determine the effect of valproic acid (VPA) on the amounts of folded rhodopsin in a P23H mouse model and assess VPA’s neuroprotective effect in the S334ter-3 rat model.
Methods: :
Heterozygous P23H opsin mice and S334ter-3 rats were produced by previously published methods. VPA (200 mg/kg) or a placebo was administered daily (i.p.) to P23H mice, littermate controls, or C57/B6 mice every other day for two weeks. The mice were dark-adapted overnight and their eyes were then harvested in dim red light. The total folded rhodopsin was purified from each eye and quantified by UV/visible spectroscopy using our previously published methods. Separately, in the S334ter rats, either VPA (300 mg/ml) or a placebo was administered via i.p. daily, starting at PD 9. Eyes were collected at PD 21, embedded in an Epon/Araldite mixture, and sectioned at 1 µm thickness to display the entire retina along the vertical meridian. Retinal sections were examined by light microscopy and evaluated independently by three observers.
Results: :
When compared to the retinas receiving a placebo, the P23H mice treated with VPA had an approximately 30-40% increase in the amounts of folded rhodopsin, which was statistically significant. There was no substantial effect of VPA on the littermate controls or the C57/B6 mice. In the retinas of the S334ter rats treated with VPA, the outer nuclear layer (ONL) had 2-3 rows of photoreceptor nuclei in the superior retina. In contrast, animals treated with PBS had only 1 row of nuclei in the ONL of the same retinal region. Separate quantitative data showed that the ONL thickness in treated animals was significantly higher than the controls.
Conclusions: :
Systemically delivered VPA in P23H mice resulted in increased folded rhodopsin levels and in modest but significant preservation of photoreceptors in the S334ter-3 rats.
Keywords: protective mechanisms • retinal degenerations: cell biology • retinitis