title: Neural reprogramming in retinal degeneration.
abstract: OBJECTIVE
  Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration.
  
  
  METHODS
  Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP.
  
  
  RESULTS
  After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the number of bipolar cells expressing functional iGluRs was double that of normal retina.
  
  
  CONCLUSIONS
  RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some nonglutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late RP photoreceptor transplantation attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function.
authors.affiliation: Department of Ophthalmology, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah 84132. robert.marc@hsc.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marc
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Jones
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.forename: Krista
authors.initials: K
authors.lastname: Kinard
authors.forename: David W
authors.initials: DW
authors.lastname: Marshak
authors.forename: John H
authors.initials: JH
authors.lastname: Wilson
authors.forename: Theodore
authors.initials: T
authors.lastname: Wensel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lucas
mesh_terms: D000376:Agmatine / Q000378:metabolism; D025042:Amacrine Cells / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology*; D048530:Papio anubis; D010641:Phenotype; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D000376:Agmatine; C104722:glutamate receptor ionotropic, AMPA 2