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Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration

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Abstract

Diabetic retinopathy (DR) is a serious neurodegenerative disease that is induced by hyperglycaemia. Oxidative stress, inflammation and endoplasmic reticulum (ER) stress are involved in the development of DR. Sulforaphane (SF) is widely found in cruciferous plants and has a protective effect against retinal neurodegeneration in diabetes, but the mechanism is unclear. In this study, we investigated the mechanism by which SF protects against photoreceptor degeneration in diabetes. In vivo, a mouse model of diabetes was established by streptozotocin (STZ) injection, and the mice were treated with/without SF. Electroretinography (ERG) and H&E staining were used to evaluate retinal function and morphology. In vitro, 661w cells were treated with AGEs with/without SF. Cell viability and apoptosis were analysed by CCK-8 assay and flow cytometry. The expression of proteins and genes was assessed by western blot and qRT-PCR. The amplitude of the a-wave was decreased and the morphology was changed in the diabetic mice, and these changes were delayed by SF treatment. The percentage of apoptotic cells was increased and the cell viability was decreased after the treatment of 661w cells with AGEs. Moreover, the expression of GRP78, Txnip and TNFα was increased, however, this increased expression was reversed by SF treatment via AMPK pathway activation. Taken together, these data show that SF can delay photoreceptor degeneration in diabetes, and the underlying mechanism is related to the inhibition of ER stress, inflammation and Txnip expression through the activation of the AMPK pathway.

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Funding

This project has been supported by Grant No. 31371218 from the National Natural Science Foundation of China and Grant No. LQ2017005 from the Basic Scientific Research Projects of Liaoning Provincial Education Department. This project was also supported by Liaoning Provincial Program for Top Discipline of Basic Medical Sciences and National and Local Joint Engineering Research Center for Mongolian Medicine Research and Development (MDK2019041). This project was also supported by Grant NO. 2020-BS-189 from the Natural Science Foundation of Liaoning Province.

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Author notes

  1. Jinjuan Lv and Shuyin Bao contributed equally to this work.

Authors and Affiliations

  1. Department of Histology and Embryology, College of basic medicine, Dalian Medical University, Dalian, 116044, Liaoning Province, China

    Jinjuan Lv, Tianhe Liu, Limin Wei, Nina Wang, Shiyu Song, Jiao Li, Maryam Chudhary, Xiang Ren & Li Kong

  2. Medical College, Inner Mongolia University for Nationalities, Tongliao, 028300, Inner Mongolia, China

    Shuyin Bao

  3. Department of Anesthesia, Dalian Medical University, Dalian, 116044, Liaoning Province, China

    Dongming Wang & Weikang Ye

Authors
  1. Jinjuan Lv
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  2. Shuyin Bao
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  3. Tianhe Liu
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  4. Limin Wei
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  5. Dongming Wang
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  6. Weikang Ye
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  7. Nina Wang
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  8. Shiyu Song
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  9. Jiao Li
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  10. Maryam Chudhary
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  11. Xiang Ren
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  12. Li Kong
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Contributions

Xiang Ren and Li Kong conceived and designed the experiments. Jinjuan Lv and Shuyin Bao performed the experiments and analysed the data. Tianhe Liu Limin Wei, Dongming Wang, Weikang Ye, Shiyu Song, Nina Wang, Jiao Li and Maryam Chudhary contributed some experiments, reagents, materials and analytical tools. Jinjuan Lv wrote the manuscript.

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Correspondence to Xiang Ren or Li Kong.

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The authors declare that they have no conflict of interest.

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All protocols and use of laboratory animals were approved by the Animal Care Committee of Dalian Medical University Laboratory Animal Center.

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Lv, J., Bao, S., Liu, T. et al. Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration. Cell Tissue Res 382, 477–486 (2020). https://doi.org/10.1007/s00441-020-03267-w

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