Structural abnormalities of the optic nerve and retina in Huntington’s disease pre-clinical and clinical settings
File(s)
Published version
Author(s)
Mazur-Michałek, Iwona
Kowalska, Katarzyna
Zielonka, Daniel
Leśniczak-Staszak, Marta
Pietras, Paulina
Type
Journal Article
Abstract
Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies.
Date Issued
2022-05-13
Date Acceptance
2022-05-11
Citation
International Journal of Molecular Sciences, 2022, 23 (10)
ISSN
1422-0067
Publisher
MDPI AG
Journal / Book Title
International Journal of Molecular Sciences
Volume
23
Issue
10
Copyright Statement
© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/)
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/)
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
102944/Z/13/Z
102944/Z/13/Z
RDF01
RDF01
Subjects
Huntington’s disease
mouse models
ocular neurodegeneration
optic nerve
optical coherence tomography
transmission electron microscopy
Animals
Huntington Disease
Mice
Nerve Fibers
Optic Disk
Optic Nerve
Retina
Nerve Fibers
Optic Nerve
Optic Disk
Retina
Animals
Mice
Huntington Disease
Chemical Physics
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Publication Status
Published
Article Number
ARTN 5450