Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer's disease

Bevan, Ryan J., Hughes, Tim R. ORCID: https://orcid.org/0000-0003-2348-3490, Williams, Pete A., Good, Mark A. ORCID: https://orcid.org/0000-0002-1824-1203, Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676 and Morgan, James E. ORCID: https://orcid.org/0000-0003-4075-7676 2020. Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer's disease. Acta Neuropathologica Communications 8 (1) , 216. 10.1186/s40478-020-01094-2

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Abstract

Neuronal dendritic and synaptic pruning are early features of neurodegenerative diseases, including Alzheimer’s disease. In addition to brain pathology, amyloid plaque deposition, microglial activation, and cell loss occur in the retinas of human patients and animal models of Alzheimer’s disease. Retinal ganglion cells, the output neurons of the retina, are vulnerable to damage in neurodegenerative diseases and are a potential opportunity for non-invasive clinical diagnosis and monitoring of Alzheimer’s progression. However, the extent of retinal involvement in Alzheimer’s models and how well this reflects brain pathology is unclear. Here we have quantified changes in retinal ganglion cells dendritic structure and hippocampal dendritic spines in three well-studied Alzheimer’s mouse models, Tg2576, 3xTg-AD and APPNL-G-F. Dendritic complexity of DiOlistically labelled retinal ganglion cells from retinal explants was reduced in all three models in an age-, gender-, and receptive field-dependent manner. DiOlistically labelled hippocampal slices showed spine loss in CA1 apical dendrites in all three Alzheimer’s models, mirroring the early stages of neurodegeneration as seen in the retina. Morphological classification showed that loss of thin spines predominated in all. The demonstration that retinal ganglion cells dendritic field reduction occurs in parallel with hippocampal dendritic spine loss in all three Alzheimer’s models provide compelling support for the use of retinal neurodegeneration. As retinal dendritic changes are within the optical range of current clinical imaging systems (for example optical coherence tomography), our study makes a case for imaging the retina as a non-invasive way to diagnose disease and monitor progression in Alzheimer’s disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences Psychology Medicine
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Publisher:	BioMed Central
ISSN:	2051-5960
Date of First Compliant Deposit:	6 January 2021
Date of Acceptance:	23 November 2020
Last Modified:	05 May 2023 13:20
URI:	https://orca.cardiff.ac.uk/id/eprint/137355

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