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

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.

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

“…Administration of antioxidants has in some cases improved PR survival. Rs1 tm1Web homozygous females or hemizygous males fed a diet high in DHA [493] or Pde6b rd10 mice fed lutein and zeaxanthin [494] showed a significant PR preservation. Further, injections of a mixture of antioxidants-alpha tocopheral, ascorbic acid, alpha-lipoic acid, and/or Mn(III)tetrakis porphyrin-were able to slow the loss of cone/rod PRs in Pde6b rd1 [495], and Pde6b rd10 mice and in mice with a rhodopsin Q344ter mutation [492].…”

Wolfberry‐derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways

“…Among carotenoid in wolfberry, ZD accounts for 31%-56% of them (Peng et al, 2005), followed by β-cryptoxanthin monopalmitate, zeaxanthin monopalmitate, β-carotene and zeaxanthin (Inbaraj et al, 2008). The effect of zeaxanthin (with lutein) on retinal health was tested in several animals and clinical studies, and it has been shown to have a protective role (Sahin et al, 2019;Yu et al, 2018). For example, feeding rd10 mice with lutein and zeaxanthin isomers from P6 to P20 increased the survival of photoreceptors by around 60% (Yu et al, 2018).…”

“…The effect of zeaxanthin (with lutein) on retinal health was tested in several animals and clinical studies, and it has been shown to have a protective role (Sahin et al, 2019;Yu et al, 2018). For example, feeding rd10 mice with lutein and zeaxanthin isomers from P6 to P20 increased the survival of photoreceptors by around 60% (Yu et al, 2018). However, ZD, the di-ester form of zeaxanthin, which is the major carotenoid in wolfberry, has an advantage over zeaxanthin.…”

“…Another group of major constituents in wolfberry are carotenoids, which include zeaxanthin and zeaxanthin dipalmitate (ZD), the di-esters of zeaxanthin. Zeaxanthin, together with lutein, have protective effects on retina in many animal and clinical studies (Johnson, 2014;Sahin et al, 2019;Yu et al, 2018). With multiple conjugated double bonds in its chemical structure as zeaxanthin, ZD has a strong anti-oxidant function as demonstrated by its strong ability to scavenge free radicals and protect liver cells against several liver diseases (Gao et al, 2019;Xiao et al, 2014).…”

Progesterone, Lipoic Acid, and Sulforaphane as Promising Antioxidants for Retinal Diseases: A Review

“…Due to the antioxidant capacity of LA, which has been argued previously, it could be a candidate for preventing the photoreceptors death. In fact, a variety of antioxidants has been tested as a treatment for RP in, both, animal [94,95,96] and human models [97,98].…”