Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease
Huntington's disease (HD) is a progressive neurological disease characterised by motor dysfunction, cognitive impairment and personality changes. Previous work in HD patients and animal models of the disease has also highlighted retinal involvement. This study characterised the changes in retin...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996111003792 |
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| author | Abrez Hussain Batcha Una Greferath Andrew I. Jobling Kirstan A. Vessey Michelle M. Ward Jess Nithianantharajah Anthony J. Hannan Michael Kalloniatis Erica L. Fletcher |
| author_facet | Abrez Hussain Batcha Una Greferath Andrew I. Jobling Kirstan A. Vessey Michelle M. Ward Jess Nithianantharajah Anthony J. Hannan Michael Kalloniatis Erica L. Fletcher |
| author_sort | Abrez Hussain Batcha |
| collection | DOAJ |
| description | Huntington's disease (HD) is a progressive neurological disease characterised by motor dysfunction, cognitive impairment and personality changes. Previous work in HD patients and animal models of the disease has also highlighted retinal involvement. This study characterised the changes in retinal structure and function early within the progression of disease using the R6/1 mouse model of HD. The retinal phenotype was observed to occur at the same time in the disease process as other neurological deficits such as motor dysfunction (by 13 weeks of age). There was a specific functional deficit in cone response to the electroretinogram and using immunocytochemical techniques, this dysfunction was found to be likely due to a progressive and complete loss of cone opsin and transducin protein expression by 20 weeks of age. In addition, there was an increase in Müller cell gliosis and the presence of ectopic rod photoreceptor terminals. This retinal remodelling is also observed in downstream neurons, namely the rod and cone bipolar cells. While R6/1 mice exhibit significant retinal pathology simultaneously with other more classical HD alterations, this doesn't lead to extensive cell loss. These findings suggest that in HD, cone photoreceptors are initially targeted, possibly via dysregulation of protein expression or trafficking and that this process is subsequently accompanied by increased retinal stress and neuronal remodelling also involving the rod pathway. As retinal structure and connectivity are well characterised, the retina may provide a useful model tissue in which to characterise the mechanisms important in the development of neuronal pathology in HD. |
| first_indexed | 2024-12-13T18:57:43Z |
| format | Article |
| id | doaj.art-996c6baf695547819f0e40f1137328df |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T18:57:43Z |
| publishDate | 2012-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-996c6baf695547819f0e40f1137328df2022-12-21T23:34:45ZengElsevierNeurobiology of Disease1095-953X2012-03-01453887896Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's diseaseAbrez Hussain Batcha0Una Greferath1Andrew I. Jobling2Kirstan A. Vessey3Michelle M. Ward4Jess Nithianantharajah5Anthony J. Hannan6Michael Kalloniatis7Erica L. Fletcher8Department of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, AustraliaHoward Florey Institute, Florey Neuroscience Institutes, The University of Melbourne, Parkville 3010, Victoria, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, Australia; Howard Florey Institute, Florey Neuroscience Institutes, The University of Melbourne, Parkville 3010, Victoria, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, Australia; Centre for Eye Health and School of Optometry and Vision Science, University of New South Wales, Sydney 2052, New South Wales, AustraliaDepartment of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010, Victoria, Australia; Corresponding author at: Department of Anatomy and Cell Biology, The University of Melbourne, Grattan St, Parkville 3010, Victoria, Australia. Fax: +61 3 9347 5219.Huntington's disease (HD) is a progressive neurological disease characterised by motor dysfunction, cognitive impairment and personality changes. Previous work in HD patients and animal models of the disease has also highlighted retinal involvement. This study characterised the changes in retinal structure and function early within the progression of disease using the R6/1 mouse model of HD. The retinal phenotype was observed to occur at the same time in the disease process as other neurological deficits such as motor dysfunction (by 13 weeks of age). There was a specific functional deficit in cone response to the electroretinogram and using immunocytochemical techniques, this dysfunction was found to be likely due to a progressive and complete loss of cone opsin and transducin protein expression by 20 weeks of age. In addition, there was an increase in Müller cell gliosis and the presence of ectopic rod photoreceptor terminals. This retinal remodelling is also observed in downstream neurons, namely the rod and cone bipolar cells. While R6/1 mice exhibit significant retinal pathology simultaneously with other more classical HD alterations, this doesn't lead to extensive cell loss. These findings suggest that in HD, cone photoreceptors are initially targeted, possibly via dysregulation of protein expression or trafficking and that this process is subsequently accompanied by increased retinal stress and neuronal remodelling also involving the rod pathway. As retinal structure and connectivity are well characterised, the retina may provide a useful model tissue in which to characterise the mechanisms important in the development of neuronal pathology in HD.http://www.sciencedirect.com/science/article/pii/S0969996111003792RetinaHuntington's diseasePhotoreceptorCone opsinRemodelling |
| spellingShingle | Abrez Hussain Batcha Una Greferath Andrew I. Jobling Kirstan A. Vessey Michelle M. Ward Jess Nithianantharajah Anthony J. Hannan Michael Kalloniatis Erica L. Fletcher Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease Neurobiology of Disease Retina Huntington's disease Photoreceptor Cone opsin Remodelling |
| title | Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease |
| title_full | Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease |
| title_fullStr | Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease |
| title_full_unstemmed | Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease |
| title_short | Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease |
| title_sort | retinal dysfunction photoreceptor protein dysregulation and neuronal remodelling in the r6 1 mouse model of huntington s disease |
| topic | Retina Huntington's disease Photoreceptor Cone opsin Remodelling |
| url | http://www.sciencedirect.com/science/article/pii/S0969996111003792 |
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