Sulforaphane ameliorates photoreceptor degeneration in Pde6^rd10 mice

Abstract

Purpose : Oxidative stress and endoplasmic reticulum (ER) stress are major factors underlying photoreceptor degeneration in retinitis pigmentosa (RP). Sulforaphane (SFN) is a naturally occurring isothiocyanate, which protects against cell damage by ameliorating oxidative stress and ER stress in retina. In this study, we evaluated the efficacy of SFN on the phenotype of the Pde6^rd10 (rd10) mouse model of RP.

Methods : SFN (35 mg/kg) dissolved in saline (4 mg/ml) or equal volume of saline was administered by intraperitoneal injection to rd10 mice daily from postnatal day (P) 6 to P20. At P21, retinas were examined by electroretinography (ERG), TUNEL staining, western blot and immunohistochemistry.

Results : In comparison to vehicle-treated animals, mice treated with SFN had larger amplitude of ERG a-waves, indicative of a greater number of rods surviving in these retinas. ERG b-waves were also larger in SFN treated mice, under both dark- and light-adapted conditions, indicating that preservation of rods slowed the secondary involvement of cones. In rd10 mice, TUNEL-positive cells were mainly found in the outer nuclear layer, and their frequency was significantly lower in mice treated with SFN than with vehicle. Western blot and immunohistochemistry studies show that GRP78, the marker of ER stress, was downregulated by SFN treatment.

Conclusions : SFN exerts a beneficial impact on the rd10 mouse model of RP, which may be related to its reduction of ER stress in the outer retina. SFN treatment may be an effective means to slow photoreceptor degeneration in many forms of RP.

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