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ET Matthiessen, U Bartsch, BR Zolmajd, S Linke, M Schachner, G Richard, K Ruether; Retinal function in Na, K-ATPase Subunit ß2/ß1 knock-in mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1779.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The Na, K-ATPase is an ubiquitously expressed heterodimeric ion pump consisting of an α- (α1, α2 or α3) and a ß-subunit (ß1, ß2 or ß3). ß2-deficient mice exhibit early retinal degeneration and die at about postnatal day 18. In ß2/ß1 knock-in mice expression of ß2 is abolished, and ß1 mRNA expression from the mutated gene amounts to 15% of the normal expression of ß2 mRNA in wild types. These animals display a normal life span and exhibit a rather slow retinal degeneration. The purpose of this study was to characterize the retinal degeneration in ß2/ ß1 knock in mutants with electrophysiological techniques. Methods: In order to assess retinal function, electroretinograms (ERGs) were performed in 75 ß2/ß1 knock-in mice (ß2/ß1ki/ki) at 14, 30, 60, 90, 120, 150 and 270 days of age and in 30 age-matched wild type (ß1/ß2+/+) mice. Light- and dark-adapted ERGs were recorded using a Ganzfeld stimulus. C-waves were evoked by green light emitting diodes. Results: ERG cone responses were not detectable in ß2/ß1ki/ki mice. The scotopic ERG was significantly reduced at all developmental ages in ß2/ß1ki/ki mice when compared to ß1/ß2+/+ mice. Scotopic responses declined over time in mutants and wild types. At 150 days of age, the a-wave amplitude was reduced by 75% and 45% in ß2/ß1ki/ki and wild type mice, respectively. The decrease of the b- wave amplitude was 66% and 42%, respectively. The c-wave amplitudes were also significantly reduced in ß2/ß1ki/ki mice (p<0,001; at 14 days of age). Beyond 150 days of age, the rate of amplitude reduction accelerated leading to a barely detectable ERG in 270-day-old ß2/ß1ki/ki mice. Conclusion: Our electrophysiological findings correspond well to previously published histological findings. The progressive loss of photoreceptor cells in ß2/ß1ki/ki mice leads to a significant reduction of the outer nuclear layer thickness in 120-day-old animals, and degeneration of photoreceptor cells is almost complete in 270-day-old mutants (Weber et al. J Neurosci 18(22) p9192-203). The reduced ERG responses already in young ß2/ß1ki/ki mice may be due to an insufficient Na, K-ATPase activity, whereas at later stages, retinal function is compromised by the degenerative process. One of the most interesting results of this study is the absence of a cone ERG. It remains to be analysed whether this defect is related to an developmental deficit, an early and rapid degeneration or to a functional deficit of existing cones.
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