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N.V. Pfau, M. Altwein, K. Bumsted O'Brien, M. Kneussel, J.H. Brandstatter; Importance of NMDA Receptors for Normal Development of the Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1653.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: NMDA receptors play important roles in neuronal survival and differentiation as well as in the formation and stabilization of synapses and circuits during nervous system development. To investigate the function of NMDA receptors in retinal development, we have studied a gene targeted mouse deficient in the mandatory NMDA receptor subunit NR1 (NR1 -/-). Methods: NR1 -/- mice die at birth. To study postnatal retinal development, retinal explants, dissected at E19, were cultured in a roller incubator (organotypic culture). After 15 days in vitro (DIV 15), retinal gross anatomy, expression of synaptic markers, neurotransmitter receptors, and the morphology of the different retinal neurons was examined with immunocytochemistry in NR1 wild-type (WT) and NR1 -/- retinal cultures. Results: At E 19, no anatomical differences were noted between the NR1 -/- and the WT retinae. At DIV 15, the NR1 -/- mice, like the WT mice, had a developed retinal architecture with the characteristic lamination of three nuclear and two plexiform layers. In the NR1 -/- retina, however, the outer and the inner nuclear layer were significantly thinner compared to WT retinae. Lack of functional NMDA receptors had no obvious effect on the cellular development of amacrine, horizontal and ganglion cells and the formation of inhibitory GABAergic and glycinergic synapses. The glutamatergic system in the NR1 -/- retina was greatly perturbed, as seen in a lower number and changed distribution of glutamatergic synapses in the plexiform layers. Rod bipolar cell number was significantly reduced, and their morphology changed, in the NR1 -/- retina. Rod bipolar cells develop in the NR1 -/- culture, as shown with BrdU staning, but they undergo increased apoptosis between DIV 8 to DIV 15 (TUNEL). Conclusions: These findings suggest that lack of functional NMDA receptors in the developing retina does not globaly effect neuronal and synaptic differentiation. It selectively perturbs the development of the glutamatergic system, and that of the rod bipolar cells by increased apoptosis.
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