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GM Seigel, A Lotery, A Kummer, M Turmaine, B Davidson, J Wagner, HM Mitchison; Continued retinal function despite NCL pathology in a Cln3 knockout mouse model of Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2717.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Batten disease or JNCL, is the juvenile form of Neuronal Ceroid Lipofuscinosis, an autosomal recessive neurodegenerative disorder characterized by the accumulation of an autofluorescent lipopigment in many cell types. Since retinal degeneration is an early consequence of Batten disease, we examined the eyes of Cln3 knockout mice, along with heterozygotes and appropriate controls, to determine whether or not the Cln3 defect would lead to characteristic retinal degeneration and visual loss in this mouse model. Methods: Control, heterozygote, and cln3- knock-out mice (aged one to twenty months) were perfused, and the eyes preserved in 4% paraformaldehyde. The eyes were embedded in paraffin and cut into 4 micron tissue sections for immunohistochemical analysis. Apoptosis was detected using TUNEL-in situ and ssDNA analyses, as well as electron microscopy. The presence of intracellular storage material was visualized by Periodic Acid-Schiff (PAS), and soybean agglutinin (SBA) staining, as well as by autofluorescence and electron microscopy. Retinal appearance and function were assessed by fundus photography and electroretinogram recordings, respectively. Results: Accumulation of autofluorescent material, electron-dense intracellular inclusions, PAS and SBA-reactive material were markedly increased in Cln3 knockout retinal tissue. A low level of apoptosis was observed in the photoreceptor layer, while density of the nerve fiber layer was significantly decreased in Cln3 knockout retinae. Yet, the degree of retinal degeneration up to age 20 months was not extensive. Fundus examinations of Cln3 knockout mice revealed no significant abnormalities, while electroretinogram patterns remained robust through 11 months of age. Conclusion: It appears that late-onset accumulation of autofluorescent material, carbohydrate storage material, as well as apoptotic cell death are manifestations of the Cln3 defect that do not appear to extinguish retinal function in this mouse model of Batten disease.
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