Structural Abnormalities of the Optic Nerve and Retina in Huntington's Disease Pre-Clinical and Clinical Settings

Autor:	Iwona Mazur-Michałek, Katarzyna Kowalska, Daniel Zielonka, Marta Leśniczak-Staszak, Paulina Pietras, Witold Szaflarski, Mark Isalan, Michal Mielcarek
Přispěvatelé:	Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding
Rok vydání:	2022
Předmět:	genetic structures 0699 Other Biological Sciences Optic Disk ocular neurodegeneration Catalysis Retina Inorganic Chemistry Mice Nerve Fibers transmission electron microscopy 0399 Other Chemical Sciences Animals mouse models Physical and Theoretical Chemistry Molecular Biology Spectroscopy 0604 Genetics optical coherence tomography Chemical Physics Organic Chemistry Optic Nerve General Medicine eye diseases Computer Science Applications Huntington Disease sense organs Huntington’s disease optic nerve
Zdroj:	International Journal of Molecular Sciences; Volume 23; Issue 10; Pages: 5450
ISSN:	1422-0067
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5efb4072cb0999339f6dd373a7989f9b https://pubmed.ncbi.nlm.nih.gov/35628260 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.