Is mouse retinal affectation by HTT cag expansion suitable for modelling the neuroinflammatory component of Huntington’s disease?

  1. Valor, Luis M 1
  2. Cano-Cano, Fátima 2
  3. Gallardo-Orihuela, Andrea 2
  4. Martín-Loro, Francisco 2
  5. González-Montelongo, M Carmen 2
  6. Hervás-Corpión, Irati 2
  7. Villa, Pedro de la 3
  8. Arroba, Ana I 2
  1. 1 Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) – Hospital General Universitario Dr. Balmis, Spain
  2. 2 Instituto de Investigación e Innovación de Ciencias Biomédicas de Cádiz (INiBICA) – Hospital Universitario Puerta del Mar, Spain
  3. 3 Instituto Ramón y Cajal de Investigación Sanitaria – Universidad de Alcalá de Henares, Spain
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Actas:
B: Models for HD

Año de publicación: 2022

Tipo: Aportación congreso

DOI: 10.1136/JNNP-2022-EHDN.42 GOOGLE SCHOLAR lock_openAcceso abierto editor

Resumen

Background In Huntington’s disease (HD), striatal dysfunction has been intensively studied in mouse models as basal ganglia are the main brain areas affected in patients, and explains the most evident symptomatology. Nonetheless, cumulative evidences indicate that retina can also be functionally altered with consequences for visual function and circadian rhythms. In addition, the retina is the exposed part of the central nervous system that can be used for non-invasive monitoring of patients’ health. Aims To firmly establish the retina as an appropriate tissue for HD studies, we need to link its cellular and molecular alterations with those of the inner brain. Methods We combined optical coherence tomography, electroretinograhy, RNA-seq, transcriptomics meta-analysis and immunodetection assays to assess R6/1 and zQ175 mice. Results We confirmed that the retina of R6/1 mice were functionally and morphologically affected, and suffered a rearrangement of its transcriptome as extensively deregulated as the R6/1 striatum. Cell-enriched genes were downregulated in both tissues, but a neuroinflammation signature was specific of the R6/1 retina, through the activation of astrocytes and microglia that was not significant in the striatum. These changes did not follow a regular inflammatory process and were accompanied by a differential impairment of the autophagy system between both tissues. The most important findings were validated in the zQ175 strain. Conclusions The retina deserve further investigation as a model for the neuroinflammatory component of HD and neurodegeneration.