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Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina

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Abstract

Lutein injection is a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate its protective effects in retinal ganglion cells (RGCs) against N-methyl-d-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p–c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.

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Abbreviations

RGCs:

Retinal ganglion cells

ERG:

Electroretinograms

phNR:

Photic negative response

RIPA:

Radio immunoprecipitation assay

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

PVDF:

Polyvinylidene fluoride

ECL:

Electrochemiluminescence

AkT:

Protein kinase B/PKB

ERK:

Extracellular signal-regulated kinase

GSK-3β:

Glycogen synthase kinase-3β

MAPK:

Mitogen-activated protein kinases

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Acknowledgments

This work was supported by grants from the National Program on Key Basic Research Project (973 Program No. 2011CB707501), and the National Natural Science Foundation of China (Nos. 81371442 and 81471236).

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Authors and Affiliations

  1. Key Laboratory of State Administration of Traditional Chinese Medicine of China, Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong Province, China

    Chanjuan Zhang, Zhen Wang, Jiayi Zhao, Qin Li, Cuiqin Huang, Lihong Zhu & Daxiang Lu

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  1. Chanjuan Zhang
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  2. Zhen Wang
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  3. Jiayi Zhao
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Correspondence to Daxiang Lu.

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Zhang, C., Wang, Z., Zhao, J. et al. Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina. Cell Mol Neurobiol 36, 531–540 (2016). https://doi.org/10.1007/s10571-015-0231-5

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