Fine‐structural analysis and connexin expression in the retina of a transgenic model of Huntington's disease

Abstract

Recent studies indicate that the visual system appears more frequently affected in polyglutamine diseases than expected previously. Here, we investigated retinal degenerations in adult transgenic R6/2 mice, a model for Huntington's disease (HD). Light microscopical analysis revealed retinal dystrophy all over the retina, with central areas showing major effects. Electron microscopical analysis showed strong degenerations of outer and inner photoreceptor segments, shrinkage of photoreceptor cell somata, and signs of degeneration in photoreceptor terminals in the outer plexiform layer. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling showed hints of apoptosis. Mutant huntingtin and ubiquitin were expressed in all classes of retinal neurons, the pigment epithelium, and to a minor extent in neuropil structures. For investigating possible links to functional impairments in the rod-cone pathway, expression levels of three connexins (Cx) were compared in R6/2 and wildtype mice retinae. In R6/2 mice, expression of Cx36, the major neuronal connexin in the retina, was slightly reduced in the outer plexiform layer, indicating affected photoreceptor terminals as detected at the electron microscopical level. In contrast, Cx45, a putative neuronal connexin in the retina, was remarkably reduced in the inner plexiform layer of R6/2 mice. This result corresponded to fainter signals of Cx45 mRNA as documented by in situ hybridization and to a lower level of mCx45 cDNA as obtained by polymerase chain reaction after reverse transcription, suggesting functional deficits in spatial processing of Cx45-mediated gap junction coupling due to transgene-induced retinal degenerations. Thus, it is important to clarify the meaning of visual involvement in HD.

Optical coherence tomography findings in Huntington’s disease: a potential biomarker of disease progression

“…However, The HD group has been analysed as a whole, and also separated into Manifest HD and pre-manifest HD groups. p values have been given for comparisons between the complete HD group and control participants * Denotes significance J Neurol drosophila and mouse models of HD, present with severe neuropathology, including progressive disorganisation of the photoreceptor layer and retinal dysfunction suggesting that the retina may exhibit the same neuronal pathology as the rest of the brain [39,[42][43][44][45]. In our study, inspection of OCT images did not reveal any obvious photoreceptor abnormalities.…”

Cellular and subcellular localization of Huntington aggregates in the brain of a rat transgenic for Huntington disease

“…Rats taken for conventional electron microscopy were fixed with 2.5% glutaraldehyde and 1% paraformaldehyde in 0.1 M sodium phosphate for 20 minutes at 38°C as described previously (Petrasch-Parwez et al, 2004). Removed brains were adjusted in plexiglass frames (as described above) and cut into 2-mm-thick (for rats) or 1.5-mm-thick (for mice) coronal slices.…”

Exome Sequencing RevealsAGBL5as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families

“…and transcardially perfused with 4% paraformaldehyde as described. 32 After fixation, eyes were rinsed in phosphatebuffered saline (PBS), immersed overnight in 30% saccharose in PBS, covered with Tissue-Tek OCT (Sakura Finetek, Heppenheim, Germany), shock-frozen in 8% methylcylcohexan in 2-methylbutan (v/v; À808C) and stored at À808C until used. Peroxidase immunohistochemistry was performed on 12lm Paraffin (human retinae) and cryosections (mice retinae) with the polyclonal anti-AGBL5 antibody (1:100; NBP1-83616, Novus Biologicals, Littleton, CO, USA) and the polyclonal goat anti-CCP5-antibody (1:1000; T-20, Santa Cruz Biotechnology, Inc.).…”