title: Early retinal function deficit without prominent morphological changes in the R6/2 mouse model of Huntington's disease.
abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder that primarily affects the medium-size GABAergic neurons of striatum. The R6/2 mouse line is one of the most widely used animal models of HD. Previously the hallmarks of HD-related pathology have been detected in photoreceptors and interneurons of R6/2 mouse retina. Here we aimed to explore the survival of retinal ganglion cells (RGCs) and functional integrity of distinct retinal cell populations in R6/2 mice. The pattern electroretinography (PERG) signal was lost at the age of 8 weeks in R6/2 mice in contrast to the situation in wild-type (WT) littermates. This defect may be attributable to a major reduction in photopic ERG responses in R6/2 mice which was more evident in b- than a-wave amplitudes. At the age of 4 weeks R6/2 mice had predominantly the soluble form of mutant huntingtin protein (mHtt) in the RGC layer cells, whereas the aggregated form of mHtt was found in the majority of those cells from the 12-week-old R6/2 mice and onwards. Retinal astrocytes did not contain mHtt deposits. The total numbers of RGC layer cells, retinal astrocytes as well as optic nerve axons did not differ between 18-week-old R6/2 mice and their WT controls. Our data indicate that mHtt deposition does not cause RGC degeneration or retinal astrocyte loss in R6/2 mice even at a late stage of HD-related pathology. However, due to functional deficits in the rod- and cone-pathways, the R6/2 mice suffer progressive deficits in visual capabilities starting as early as 4 weeks; at 8 weeks there is severe impairment. This should be taken into account in any behavioral testing conducted in R6/2 mice.
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Vilnius Gediminas Technical University, Department of Biochemistry, Vilnius, Lithuania; State Research Institute for Innovative Medicine, Vilnius, Lithuania; Experimentica Ltd., Kuopio, Finland.
authors.forename: Symantas
authors.initials: S
authors.lastname: Ragauskas
authors.affiliation: Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Henri
authors.initials: H
authors.lastname: Leinonen
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Experimentica Ltd., Kuopio, Finland.
authors.forename: Jooseppi
authors.initials: J
authors.lastname: Puranen
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Rönkkö
authors.affiliation: Department of Electronics and Communications Engineering, BioMediTech, Tampere University of Technology, Tampere, Finland.
authors.forename: Soile
authors.initials: S
authors.lastname: Nymark
authors.affiliation: Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Kestutis
authors.initials: K
authors.lastname: Gurevicius
authors.affiliation: Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Lipponen
authors.affiliation: Charles River DRS Finland, Kuopio, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kontkanen
authors.affiliation: Charles River DRS Finland, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Puoliväli
authors.affiliation: Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Experimentica Ltd., Kuopio, Finland.
authors.forename: Giedrius
authors.initials: G
authors.lastname: Kalesnykas
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins