Retinal Functional and Structural Changes in the 5xFAD Mouse Model of Alzheimer’s Disease

Jeremiah K.H. Lim, Qiao Xin Li, Zheng He, Algis J. Vingrys, Holly R. Chinnery, Jamie Mullen, Bang V. Bui, Christine T.O. Nguyen

Research output: Contribution to journalArticle

Abstract

Alzheimer’s disease is characterized by the aberrant deposition of protein in the brain and is the leading cause of dementia worldwide. Increasingly, there have been reports of the presence of these protein hallmarks in the retina. In this study, we assayed the retina of 5xFAD mice, a transgenic model of amyloid deposition known to exhibit dementia-like symptoms with age. Using OCT, we found that the retinal nerve fiber layer was thinner in 5xFAD at 6, 12, and 17 months of age compared with wild-type littermates, but the inner plexiform layer was thicker at 6 months old. Retinal function showed reduced ganglion cell responses to light in 5xFAD at 6, 12, and 17 months of age. This functional loss was observed in the outer retina at 17 months of age but not in younger mice. We showed using immunohistochemistry and ELISA that soluble and insoluble amyloid was present in the retina and brain at all ages. In conclusion, we report that amyloid is present in brain and retina of 5xFAD mice and that the pattern of neuronal dysfunction occurs in the inner retina at the early ages and progresses to encompass the outer retina with age. This implies that the inner retina is more sensitive to amyloid changes in early disease and that the outer retina is also affected with disease progression.

Original languageEnglish
Article number862
Number of pages13
JournalFrontiers in Neuroscience
Volume14
DOIs
Publication statusPublished - 13 Aug 2020

Bibliographical note

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted,provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Keywords

  • Alzheimer’s disease
  • electroretinography
  • mouse
  • optical coherence tomography
  • retina

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    Lim, J. K. H., Li, Q. X., He, Z., Vingrys, A. J., Chinnery, H. R., Mullen, J., Bui, B. V., & Nguyen, C. T. O. (2020). Retinal Functional and Structural Changes in the 5xFAD Mouse Model of Alzheimer’s Disease. Frontiers in Neuroscience, 14, [862]. https://doi.org/10.3389/fnins.2020.00862