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S. Haverkamp, E. Claes, P. Humphries, M. Biel, M. Seeliger; Morphological Alterations in the Retina of CNG3-/- / Rho-/- Double Mutant Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2830.
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Purpose: Due to the lack of both functional cones (deletion of the CNG3 channel) and rods (absence of rod opsin), CNG3-/- / Rho-/- double knockout (DKO) mice are unable to sense light with their photoreceptors. By comparing the retinal morphology of these animals with single knockout and wild-type animals, we can examine the role of functional photoreceptors in postnatal development. Methods: Shortly fixed tissue (4% paraformaldehyde, 15 min) was processed for immunofluorescence labeling using antibodies against blue opsin, calbindin, PKCα, NK3R, bassoon, mGluR6 and GluR1. For electron microscopy, longer fixed tissue with 0.5% glutaraldehyde was used. Results: The absence of photoreceptor function in DKO mice was documented by the lack of any electroretinographic (ERG) responses. Microscopically, rod degeneration begins at about postnatal week (PW) 4 and leads to an almost complete loss of both rods and cones by PW12. Between PW4 and PW7, cones as well as horizontal cells and rod bipolar cells undergo a remarkable process of neurite sprouting. In the outer plexiform layer (OPL), the number of rod terminals decreases, but the surviving ones show an increase in the number of the synaptic ribbons and postsynaptic elements. Postsynaptic receptors like GluR1 and mGluR6 are synaptically clustered until PW7. Morphological alterations in the inner retina appear at later stages; until PW10 the inner retina appears normal. Conclusions: CNG3-/- / Rho-/- DKO mice show a progressive degeneration of all photoreceptors within three months after birth. However, during the first weeks until PW7, presynaptic markers and postsynaptic glutamate receptors are expressed in the OPL, suggesting that neurotransmission could take place. This indicates that functional photoreceptors are not required as a developmental stimulus up to this point.
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