title: Vesicular glutamate transporter 3 in age-dependent optic neuropathy.
abstract: OBJECTIVE
  To determine retinal vesicular glutamate transporter 3 (VGLUT3) expression alterations in a mouse model of progressive optic neuropathy (glaucoma).
  
  
  METHODS
  Tissue specimens were obtained from age-matched DBA/2J and control C57BL/6J mice for western blot analysis. Enucleated globes from DBA/2J, C57BL/6J, and BALB/cJ mice were fixed in formalin, paraffin-embedded, and sectioned for VGLUT3 protein localization.
  
  
  RESULTS
  western blot analysis of the control retinas revealed the expression of a ~55 kDa immunoreactive VGLUT3 protein that is to be expected in tissues such as retina, brain, liver, heart, and kidney tissue, but not in intestinal or lung tissue. Furthermore, a strong ~130 kDa immunoreactive VGLUT3 isoform that is restricted to the central nervous system (the brain and retinas) was also identified in the controls, but was not detected in the DBA/2J retinas. Immunofluorescence microscopy showed a lack of VGLUT3 expression in the synapses between amacrine and retinal ganglion cells in DBA/2J retinas, in contrast to its strong expression in the C57BL/6J and BALB/cJ controls.
  
  
  CONCLUSIONS
  Our results implicate the dysregulated expression of a central nervous system-specific VGLUT3 isoform as a predisposing factor in the development of optic neuropathy in DBA/2J mice, a spontaneous mouse model of glaucoma. In striking parallel to the visual system defects of glaucomatous DBA/2J mice, the inner ear of VGLUT3 knockout mice displays a progressive loss of inner hair cell to spiral-ganglion neuron synapses. A significant reduction in the number of spiral-ganglion neurons leads to age-associated deafness. Thus, we propose that the absence of this biochemically uncharacterized 130 kDa VGLUT3 isoform in the DBA/2J retina is a predisposing factor in synaptic instability, and a contributing factor in the age-dependent and progressive loss of ganglion cells projecting to the brain.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL, USA.
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Munguba
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Camp
authors.forename: Miguel
authors.initials: M
authors.lastname: Risco
authors.forename: Mary L
authors.initials: ML
authors.lastname: Tapia
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Richard K
authors.initials: RK
authors.lastname: Lee
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008856:Microscopy, Fluorescence / Q000379:methods; D009901:Optic Nerve Diseases / Q000378:metabolism*; D020033:Protein Isoforms; D012160:Retina / Q000378:metabolism; D013045:Species Specificity
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D020033:Protein Isoforms; C504941:Slc17a8 protein, mouse