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R. Barhoum, A. Laguna, M. Arbones, P. de la Villa; Altered Retinal Morphogenesis and Function in Dyrk1A Deficient Mouse . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5241.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: DYRK1A gene is located in human chromosome 21. Overexpression of this gene has been proposed to contribute to mental retardation in Down syndrome patients. DYRK1A is highly expressed in several central nervous system structures including the retina. In the present work we show expression of this protein in specific neuronal populations of adult mouse retina. Retinal function in mice carrying a Dyrk1A null allele (Dyrk1A+/– mice) is addressed by electrorretinography (ERG) recordings and patch clamp recording form single cells. Methods: Immunohistochemistry for specific retinal cells was performed on Dyrk1A+/– retinal sections. Full flash ERG was also performed on these mutant mice. Patch clamp recording was performed on retinal slices and isolated bipolar cells; currents induced by retinal neurotransmitters were tested on bipolar cells form Dyrk1A deficient mice. All experiments were performed in Dyrk1A+/– mice and their control littermates. Results: Dyrk1A+/– mice have smaller eyes and thinner retinae than their control littermates. Although the general laminar structure is maintained, the number of cells in inner nuclear (INL) and ganglion cell (GCL) layers is severely reduced. In contrast, the number of photoreceptors is not altered. Immunohistochemical studies revealed decreased numbers of particular cell populations in the INL (rod bipolar cells and Müller glial cells) and in the GCL (ganglion cells) of Dyrk1A+/– mice. In addition, changes in the morphology of neuronal processes were observed in both, outer and inner plexiform layers. Electroretinographic recordings in these mice showed severe attenuations in rod b–wave amplitudes when comparing with controls, which is consistent with the reduced rod bipolar cell counts. Currents induced by glutamate, GABA or Glycine in rod bipolar cells did not show significant changes between Dyrk1A+/– mice and their control littermates. Conclusions: All together, our findings show that Dyrk1A dose reduction causes alterations in the morphology of the retina leading to a severe functional defect.
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