title: Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.
abstract: The Pde6b(rd10) (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6b(rd10) (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5.
authors.affiliation: University of Houston, College of Optometry, Houston, Texas 77204, USA.
authors.forename: M Joseph
authors.initials: MJ
authors.lastname: Phillips
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Otteson
authors.forename: David M
authors.initials: DM
authors.lastname: Sherry
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology; D051248:Retinal Horizontal Cells / Q000166:cytology / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050598:Vesicular Glutamate Transport Protein 1; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse
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