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A14 Retinal and striatal profiling of the r6/1 mouse model of huntington’s disease
  1. Luis M Valor1,
  2. Andrea Gallardo-Orihuela2,
  3. Fátima Cano-Cano2,
  4. Laura Gómez-Jaramillo2,
  5. Irati Hervás-Corpión2,
  6. Francisco Martín-Loro2,
  7. Pedro de la Villa3,
  8. Ana I Arroba2
  1. 1Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
  2. 2Instituto de Investigación e Innovación de Ciencias Biomédicas de Cádiz (INiBICA), Cadiz, Spain
  3. 3Instituto Ramón y Cajal de Investigación Sanitaria – Universidad de Alcalá de Henares, Madrid – Alcalá de Henares, Spain


Background There is increasing evidence that structural and functional integrity of visual pathways are compromised in Huntington’s disease (HD) mouse models and patients. The retina can be an accessible window of the CNS through non-invasive methods to monitor the health status and response to potential treatments in patients. However, no correlation has been firmly established between the molecular events occuring in the retina and in the most affected brain area by polyQ expansion, the striatum.

Aims To explore the potential of the retina as biomarkers source in HD, we need first to evaluate retinal and striatal alterations.

Methods After confirming the visual dysfunction of R6/1 mice in electroretinogram records, we performed a time-course analysis of gene and protein expression of markers related with HD, inflammation and autophagy in retina and striata of mutant mice compared to wild-type littermates, that was complemented with transcriptomics analysis.

Results Downregulation of genes previously associated with HD (Penk and Plk5) took earlier in the striatum compared to retina. However, degeneration-related markers were prominent in the retina compared to the timid observations in the striatum, and showed a pronounced progression until extensive gliosis and microglia activation in advance stages. The autophagy machinery was impaired in both tissues but p62 and LC3-I/II exhibited different protein patterns. The RNA-seq analysis identified extensive transcriptional changes in the retina of mutant mice that were comparable to those observed in the striatum of the same animals. This analysis confirmed the time-course results and the tissue-specific nature of the molecular alterations that are linked to HD.

Conclusions The prominent presence of degeneration-related markers in the retina of R6/1 mice justifies further exploration of this tissue in other animal and cellular models.

  • retina
  • striatum
  • mRNA
  • protein
  • autophagy
  • inflammation
  • transcriptional signatures

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