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

Visual changes are some of the earliest symptoms that patients with Alzheimer's disease (AD) experience. Pathophysiological processes such as amyloid-beta 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 x FAD mouse model of AD. We used 8-month-old female 5 x 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 x FAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U-C-13] glucose and analyzed tissue extracts by gas chromatography-mass spectrometry. We found that the retinas of 5 x FAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5 x FAD retinas but no changes in the expression of markers of Muller 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.

Automated summary

Visual changes are among the earliest symptoms observed in patients with Alzheimer's disease (AD). Research has shown that there are pathophysiological processes occurring in the retina of AD patients and animal models, including amyloid-beta plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells. Studies on the 5xFAD mouse model have revealed that there may be metabolic alterations in the retina of AD, which could impact the activity and survival of retinal ganglion cells.