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Maarten Kamermans, Ralph Florijn, Trijntje Sjoerdsma, Jan Klooster, Thomas A. Ray, Robert K. Koenekoop, Neal S. Peachey, Ronald G. Gregg, Arthur Bergen; Gpr179 Is Required For Depolarizing Bipolar Cell Function And Is Mutated In Autosomal Recessive Complete Congenital Stationary Night Blindness. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3157.
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Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by non-progressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. A spontaneous mutation in GPR179 in mouse leads to a no-b-wave ERG phenotype suggestive for block of the ON-bipolar cell pathway. Here we directly test in zebrafish whether downregulation of GPR179 expression leads to a no b-wave phenotype and whether mutations in GPR179 in man lead to cCSNB.
Gene expression was down regulated in zebrafish by using morpholino injection of embryos and the ERGs were measured 4-5 days later. Immunocytochemistry was performed on post mortem human retinas using standard techniques. The 11 exons and flanking splice sites of the human GPR179 were sequenced in 44 cCSNB patients using direct Sanger sequencing.
Functional knock-down of GPR179 expression in zebrafish led to a marked reduction in the amplitude of the ERG b-wave. This result is qualitatively similar to those obtained with nyctalopin knockdown, which is another protein involved in the ON-bipolar cell signaling cascade. In human retinas GPR179 immunoreactivity was found at the tips of the ON-Bipolar cell dendrites, on a similar location as mGluR6 and TrpM1. Sequence analyses of the GPR179 gene in 44 patients with cCSNB identified 2 that had GPR179-inactivating mutations.
Our results demonstrate that GPR179 plays a critical role in DBC signal transduction and expands our understanding of the mechanisms that mediate normal rod vision.
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