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Decreased Glucose Metabolism and Glutamine Synthesis in the Retina of a Transgenic Mouse Model of Alzheimer's Disease

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  • Anna Luna Mølgaard Tams
  • Berta Sanz-Morello
  • Emil Winther Westi
  • Zaynab Ahmad Mouhammad
  • Jens Velde Andersen
  • Kristine Karla Freude
  • Rupali Vohra
  • Jens Hannibal
  • Blanca Irene Aldana
  • Miriam Kolko
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Visual changes are some of the earliest symptoms that patients with Alzheimer's disease (AD) experience. Pathophysiological processes such as amyloid-β plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells (RGCs) have been detected in the retina of AD patients and animal models. However, little is known about the molecular processes that underlie retinal neurodegeneration in AD. The cellular architecture and constant sensory activity of the retina impose high metabolic demands. We thus hypothesized that energy metabolism might be compromised in the AD retina similarly to what has been observed in the AD brain. To address this question, we explored cellular alterations and retinal metabolic activity in the 5 × FAD mouse model of AD. We used 8-month-old female 5 × FAD mice, in which the AD-related pathology has been shown to be apparent. We observed that RGC density is selectively affected in the retina of 5 × FAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U-13C] glucose and analyzed tissue extracts by gas chromatography-mass spectrometry. We found that the retinas of 5 × FAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5 × FAD retinas but no changes in the expression of markers of Müller glia, the main glial cell type responsible for glutamate uptake and glutamine synthesis in the retina. These findings suggest that AD presents with metabolic alterations not only in the brain but also in the retina that may be detrimental to RGC activity and survival, potentially leading to the visual impairments that AD patients suffer.

Original languageEnglish
JournalCellular and Molecular Neurobiology
Volume42
Issue number1
Pages (from-to)291-303
Number of pages13
ISSN0272-4340
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

    Research areas

  • Alzheimer's disease, Cellular metabolism, Neurodegeneration, Retina, Retinal ganglion cells

ID: 71923153