Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6b rd10 Mouse Model of Retinitis Pigmentosa.

Minzhong Yu,Craig Beight,Weiming Yan

doi:10.1155/2018/4374087

Minzhong Yu, Craig Beight + Show 1 more

Open Access

https://doi.org/10.1155/2018/4374087

Copy DOI

Abstract

Purpose Lutein, RR-zeaxanthin, and RS-zeaxanthin (L-Z) are antioxidants which can reduce endoplasmic reticulum stress (ERS) and oxidative stress (OS), and ameliorate neurodegenerative diseases. However, their treatment effect in the Pde6brd10 (rd10) mouse model of retinitis pigmentosa (RP) and the underlying cellular mechanisms have not been studied. ERS is an important factor which causes photoreceptor apoptosis. The aim of the current project is to test the treatment effect of L-Z in rd10 mice and to investigate the underlying molecular mechanisms of ERS. Methods L-Z (Lutemax 2020, 10 mg/kg) diluted in sunflower oil (SFO, 1 mg/ml) or the same volume of SFO was administrated via gavage from postnatal day 6 (P6) to P20 daily in L-Z group (n=5) or SFO group (n=6) of rd10 mice. At P21, electroretinography (ERG) was performed to show the functional change of retinas. 78 kDa glucose-regulated protein (GRP78) and endoplasmic reticulum protein 29 (ERp29) were tested by western blot and immunostaining. Results The ERG amplitudes were larger in the L-Z group than those of the SFO group in all flash luminances of dark-adapted and light-adapted ERG (all p < 0.01). Western blot revealed that GRP78 in the retinas of the L-Z group was significantly downregulated compared to that of the SFO group (p < 0.01). Meanwhile, the retinal ERp29 protein was significantly upregulated in the L-Z treatment group than that of the SFO group (p < 0.01). Conclusions L-Z provide protection to the photoreceptors of rd10 mouse model of RP, which is probably associated with the reduction of ERS.

Highlights

Retinitis pigmentosa (RP) is an inherited retinal degenerative disease which affects one in 3500-5000 individuals [1]
In dark-adapted ERG, the a-wave is the response from rod or rod/cone photoreceptors, and the b-wave is mainly from bipolar cells of the rod or rod/cone pathways, which is affected by the output of rod or rod/cone photoreceptors
The b-wave of the light-adapted ERG is from bipolar cells of the cone pathway, which is affected by the output of cone photoreceptors

Summary

Introduction

Retinitis pigmentosa (RP) is an inherited retinal degenerative disease which affects one in 3500-5000 individuals [1]. The common clinical symptoms of RP include night blindness and progressive vision loss from peripheral to central vision due to the degeneration of rod and cone photoreceptors, which could eventually lead to irreversible blindness [2]. It was found that the death of cone as well as rod may be due to OS [3] and ERS [4]. As RP is a kind of disease resulting from mutant genes, increasing knowledge of the causative genes with the associated biochemical pathogenesis have been gained, and gene therapy has emerged as one of the most potential treatments for RP [5, 6]. It is still not feasible to correct all RP mutations. It is necessary to study pharmacological intervention that targets the common and major cellular signaling pathways of the pathogenesis of RP to control retinal degeneration [11]

Objectives

Methods

Results

Conclusion