Retinal dysfunction in Huntington's disease mouse models concurs with local gliosis and microglia activation
Fátima Cano-Cano1, Francisco Martín-Loro1, Andrea Gallardo-Orihuela1
1Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Unidad de Investigación, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009, Cádiz, Spain.
Scientific Reports
|February 20, 2024
Summary
Huntington's disease (HD) research can now utilize the retina. This study shows retinal changes in HD mouse models mirror brain alterations, including neuroinflammation, validating the retina as a viable research model.
Area of Science:
- Neuroscience
- Genetics
- Ophthalmology
Background:
- Huntington's disease (HD) is a genetic neurodegenerative disorder caused by CAG repeat expansion in the HTT gene.
- While striatal dysfunction is well-studied, other brain regions, like the retina, may offer insights.
- The retina's accessibility presents opportunities for noninvasive patient monitoring.
Purpose of the Study:
- To investigate retinal alterations in Huntington's disease mouse models.
- To correlate retinal changes with those in the striatum, a key affected brain area.
- To establish the retina as a suitable model for studying HD pathology and neuroinflammation.
Main Methods:
- Transcriptome analysis of retinas and striata from R6/1 HD mouse models.
- Comparison of gene expression patterns between retinal and striatal tissues.
- Confirmation of retinal neuroinflammation in the zQ175 HD mouse model.
Main Results:
- R6/1 mouse retinas exhibited extensive transcriptome rearrangement, comparable to the striatum.
- Tissue-enriched genes were downregulated in both retina and striatum.
- A distinct neuroinflammation signature and glial activation were observed in the R6/1 retina, mirroring HD patient brains.
Conclusions:
- The mouse retina serves as a valid model for Huntington's disease research.
- Retinal glial activation in HD models is comparable to that seen in human patients.
- The retina offers a promising avenue for studying HD-associated neuroinflammation and for potential noninvasive diagnostics.
