September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The effect of systemic administration of methylene blue and metformin on photoreceptor degeneration caused by selective Müller cell disruption
Author Affiliations & Notes
  • Weiyong Shen
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • Michelle X. Yam
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • So-Ra Lee
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • Ying Wang
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • Sook Chung
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • Ling Zhu
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • Mark C Gillies
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Weiyong Shen, None; Michelle Yam, None; So-Ra Lee, None; Ying Wang, None; Sook Chung, None; Ling Zhu, None; Mark Gillies, None
  • Footnotes
    Support  Australia National Health and Medical Research Council (NH&MRC, Project Grants 1028393, 1050373).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4199. doi:
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      Weiyong Shen, Michelle X. Yam, So-Ra Lee, Ying Wang, Sook Chung, Ling Zhu, Mark C Gillies; The effect of systemic administration of methylene blue and metformin on photoreceptor degeneration caused by selective Müller cell disruption. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4199.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Derangement of glucose metabolism and energy production is a potential cause of photoreceptor degeneration. Methylene blue (MB) increases shuttling of electrons through the electron transport chain in mitochondria. Metformin (MET) enhances insulin signalling. MB and MET have shown neuroprotective effects in Alzheimer’s and Parkinson’s disease. However, there is little information about their beneficial effects on retinal disease. This study aimed to test the effect of MB and MET on photoreceptor degeneration caused by selective Müller cell disruption in transgenic mice we recently generated (Shen et al. J Neurosci 2012).

Methods : Transgenic mice received daily intraperitoneal injection of MB (3mg/kg) and MET (50mg/kg) from 3 days after tamoxifen-induced Müller cell disruption and data analysis was conducted 5 days later. Changes in photoreceptors, microglia and differential expression of heat shock proteins (HSPs), glucose transporter 1 (GLUT1) and key proteins which are vital for energy homeostasis and fatty acid synthesis including acetyl-CoA carboxylase (ACC), AMP-activated protein kinase (AMPK), cytoplasmic acetyl-CoA synthetase (AceCS1) and mammalian long chain acyl-CoA synthetase (ACSL), were examined by immunofluorescent staining and Western blots.

Results : We found that systemic administration of MB and MET, either alone or in combination, prevented photoreceptor degeneration and inhibited reactive activation of microglia. The effect on photoreceptor protection was accompanied by reduced expression of HSP60 and an increase in GLUT1 expression. Further analysis showed that MB and MET treatments inhibited phosphorylation of ACC and AMPKα and increased AceCS1 but not ACSL expression.

Conclusions : Our data suggest that systemic administration of MB and MET is effective in protecting photoreceptors from degeneration. Regulation of mitochondrial function and insulin signalling may offer a novel approach for the treatment of retinal degenerative diseases.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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