Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease

Abrez Hussain Batcha, Una Greferath, Andrew I. Jobling, Kirstan A. Vessey, Michelle M. Ward, Jess Nithianantharajah, Anthony J. Hannan, Michael Kalloniatis, Erica L. Fletcher*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)887-896
Number of pages10
JournalNeurobiology of Disease
Issue number3
Publication statusPublished - Mar 2012
Externally publishedYes



  • Cone opsin
  • Huntington's disease
  • Photoreceptor
  • Remodelling
  • Retina

Cite this

Batcha, A. H., Greferath, U., Jobling, A. I., Vessey, K. A., Ward, M. M., Nithianantharajah, J., ... Fletcher, E. L. (2012). Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease. Neurobiology of Disease, 45(3), 887-896.