Carbonic anhydrase-related protein VIII is expressed in rod bipolar cells and alters signaling at the rod bipolar to AII-amacrine cell synapse in the mammalian retina

Mutation of the gene encoding carbonic anhydrase-related protein VIII (CAVIII) results in motor coordination deficits in mice and humans, due to loss of this protein in Purkinje cells of the cerebellum. Recent studies have indicated that the CAVIII gene, Car8, is also expressed in rod bipolar cells (RBCs), a critical glutamatergic neuron for scotopic vision. We investigated the localization of CAVIII in the mouse and macaque retina, and utilized the wdl mouse, which has a null mutation in the Car8 gene, to determine how the loss of CAVIII affects retinal signaling. CAVIII immunoreactivity was observed in RBCs, with particularly high staining intensity in the axon terminals. In addition, weaker staining was observed in a subset of cone bipolar cells and γ-aminobutyric acid (GABA)ergic amacrine cells. Light-evoked current and voltage responses of RBCs were not altered in the wdl mutant. However, light-evoked current responses from the AII-amacrine cell, a postsynaptic partner at the RBC ribbon synapse, were significantly larger, and more prolonged than in control mice. These changes could not be attributed to alterations in calcium current activation or inactivation, or to changes in the density of RBCs. Furthermore, no gross synaptic alterations were evident in the wdl mutant at the light or ultrastructural level. These data provide evidence that the CAVIII protein, which is highly conserved in vertebrates, is selectively expressed within neural circuits, and may be important for modulating retinal neurotransmission.