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Abstract #28127 Published in IGR 13-1
Vesicular glutamate Transporter 3 in age-dependent optic neuropathy
Munguba GC; Camp AS; Risco M; Tapia ML; Bhattacharya SK; Lee RKMolecular Vision 2011; 17: 413-419
Purpose: 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. (copyright) 2011 Molecular Vision. EMTREE DRUG INDEX TERMS (MAJOR FOCUS) vesicular glutamate transporter 3 EMTREE DRUG INDEX TERMS formaldehyde paraffin protein EMTREE MEDICAL INDEX TERMS (MAJOR FOCUS) optic nerve disease
R. K. Lee. Bascom Palmer Eye Institute, University of Miami School of Medicine, 900 NW 17th Street, Miami, FL 33136, United States. RLee@med.miami.edu
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)