Effects of Valproic Acid Treatment on Retinal Degeneration in the Mature Mouse Retina

Abstract

Purpose : Our previous studies to test the effects of systemic Valproic Acid (VPA) treatment on retinal degeneration mice found that VPA-treatment accelerated photoreceptor loss in the Rd10 mouse strain. In that model, photoreceptor degeneration occurs mostly in the mature retina, and thus is more relevant to human retinal degenerations. We wanted to test additional retinal degeneration model, Rds (retinal degeneration slow), where both photoreceptor degeneration and systemic VPA-treatment would occur in the adult retina and not overlap with retinal development.

Methods : Prph2^rds/rds mice (Rds) were treated for one month with systemic VPA (daily injections IP). VPA-treated mice were compared to PBS-treated control liter mates. During the treatment regimine, retinal layer thickness was monitored in vivo, using SD-OCT (spectral domain optical coherence tomography) at the two and four week time points. Retinal morphology was also assessed after four weeks of treatment with virtual microscopy of H&E stained paraffin sections.

Results : SD-OCT analysis of retinal layer thickness showed that systemic VPA-treatment increased the rate of photoreceptor loss in VPA-treated Rds mice compared to PBS-treated liter mates over two and four weeks of treatment. Virtual microscopy confirmed that photoreceptor numbers were less in VPA-treated litermates after four weeks of treatment.

Conclusions : Systemic VPA treatment accelerates the rate of photoreceptor loss in the Rds mouse strain. Along with our previous report of VPA’s effects on photoreceptor degeneration in Pde6b^rd10/rd10 mice, our results here suggest that valproic acid can accelerate photoreceptor loss in mature retinas involving genetic defects that impact visual transduction or photoreceptor structure.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.