title: Functional integrity and modification of retinal dopaminergic neurons in the rd1 mutant mouse: roles of melanopsin and GABA.
abstract: The progressive loss of rod and cone photoreceptors in human subjects with retinitis pigmentosa causes a gradual decline in vision and can result in blindness. Current treatment strategies for the disease rely on the integrity of inner retinal neurons, such as amacrine cells, that are postsynaptic to photoreceptors. Previous work has demonstrated that a specialized subclass of retinal amacrine cell that synthesizes and releases the key neurotransmitter dopamine remains morphologically intact during the disease; however, the pathophysiological function of these neurons remains poorly understood. Here we examined spontaneous and light-evoked spike activity of genetically labeled dopamine neurons from the retinas of retinal degeneration 1 (rd1) mice. Our results indicated that rd1 dopamine neurons remained functionally intact with preserved spontaneous spiking activity and light-evoked responses. The light responses were mediated exclusively by melanopsin phototransduction, not by surviving cones. Our data also suggested that dopamine neurons were altered during photoreceptor loss, as evidenced by less spontaneous bursting activity and increased light-evoked responses with age. Further evidence showed that these alterations were attributed to enhanced GABA/melanopsin signaling to dopamine neurons during disease progression. Taken together, our studies provide valuable information regarding the preservation and functional modification of the retinal dopamine neuronal system in rd1; this information should be considered when designing treatment strategies for retinitis pigmentosa.
authors.affiliation: Eye Research Inst., Oakland Univ., 423 Dodge Hall, Rochester, MI 48309, USA.
authors.forename: Cameron L
authors.initials: CL
authors.lastname: Atkinson
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.forename: Dao-Qi
authors.initials: DQ
authors.lastname: Zhang
mesh_terms: D025042:Amacrine Cells / Q000502:physiology; D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000502:physiology*; D005074:Evoked Potentials, Visual; D055537:Light Signal Transduction; D051379:Mice; D008822:Mice, Transgenic; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000502:physiology; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D017299:Rod Opsins; D005680:gamma-Aminobutyric Acid; D000099210:Melanopsin; C517438:Pde6b protein, mouse