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Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status

Author

Listed:
  • Aidan Anderson

    (University of Birmingham)

  • Nada Alfahad

    (University of Birmingham)

  • Dulani Wimalachandra

    (University of Birmingham)

  • Kaouthar Bouzinab

    (University of Birmingham)

  • Paula Rudzinska

    (University of Birmingham)

  • Heather Wood

    (University of Birmingham)

  • Isabel Fazey

    (University of Birmingham)

  • Heping Xu

    (Queen’s University Belfast)

  • Timothy J. Lyons

    (Medical University of South Carolina
    Diabetes Free South Carolina)

  • Nicholas M. Barnes

    (University of Birmingham)

  • Parth Narendran

    (University of Birmingham)

  • Janet M. Lord

    (University of Birmingham)

  • Saaeha Rauz

    (University of Birmingham
    Birmingham & Midland Eye Centre)

  • Ian G. Ganley

    (University of Dundee)

  • Tim M. Curtis

    (Queen’s University Belfast)

  • Graham R. Wallace

    (University of Birmingham)

  • Jose R. Hombrebueno

    (University of Birmingham)

Abstract

The recovery of mitochondrial quality control (MQC) may bring innovative solutions for neuroprotection, while imposing a significant challenge given the need of holistic approaches to restore mitochondrial dynamics (fusion/fission) and turnover (mitophagy and biogenesis). In diabetic retinopathy, this is compounded by our lack of understanding of human retinal neurodegeneration, but also how MQC processes interact during disease progression. Here, we show that mitochondria hyperfusion is characteristic of retinal neurodegeneration in human and murine diabetes, blunting the homeostatic turnover of mitochondria and causing metabolic and neuro-inflammatory stress. By mimicking this mitochondrial remodelling in vitro, we ascertain that N6-furfuryladenosine enhances mitochondrial turnover and bioenergetics by relaxing hyperfusion in a controlled fashion. Oral administration of N6-furfuryladenosine enhances mitochondrial turnover in the diabetic mouse retina (Ins2Akita males), improving clinical correlates and conferring neuroprotection regardless of glycaemic status. Our findings provide translational insights for neuroprotection in the diabetic retina through the holistic recovery of MQC.

Suggested Citation

  • Aidan Anderson & Nada Alfahad & Dulani Wimalachandra & Kaouthar Bouzinab & Paula Rudzinska & Heather Wood & Isabel Fazey & Heping Xu & Timothy J. Lyons & Nicholas M. Barnes & Parth Narendran & Janet M, 2024. "Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45387-9
    DOI: 10.1038/s41467-024-45387-9
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    References listed on IDEAS

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    1. Enrique Zudaire & Laure Gambardella & Christopher Kurcz & Sonja Vermeren, 2011. "A Computational Tool for Quantitative Analysis of Vascular Networks," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-12, November.
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