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M.L. Tapia, A.S. Hackam, R.K. Lee; Differential Expression of Vesicular Glutamate Transporters in Murine Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1559.
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Glutamate is a major neurotransmitter in the retina. Glutamate vesicular transporters are responsible for loading glutamate into synaptic vesicles for glutamatergic signaling. The DBA2/J mouse model of glaucoma is associated with decreased pattern electroretinography amplitude secondary to retinal ganglion cell loss. We tested if vesicular glutamate transporter (VGLUTs) expression levels are associated with decreased retinal signaling and ganglion cell loss in DBA2/J mice eyes.
Pooled whole retinas from young, non–glaucomatous (< 3 mo. old) and from aged, glaucomatous (≥ 12 mo. old.) DBA2/J mice were homogenized and total RNA was extracted in Triazol using Qiagen RNAEasy separation columns. First strand cDNA was synthesized and used for hybridization to Affymetrix GeneChip Mouse Genome 430 2.0 gene expression microarrays to determine transcriptional levels of VGLUTs 1 and 2. Quantitative real–time PCR was used to confirm the microarray gene expression data for VGLUTs 1 and 2. Non–glaucomatous age–matched C57/BL6 mouse retinas were also used as controls. Histopathology of young, non–glaucomatous and aged, glaucomatous DBA2/J mice was examined to correlate the loss of retinal ganglion cells due to glaucoma.
Gene array data was analyzed with Affymetrix Microarray Suite 5.0 and VGLUT2 was identified as one of the most down–regulated genes differentially expressed in aged, glaucomatous DBA2/J retinas compared to young, non–glaucomatous DBA2/J retinas and to age–matched C57/Bl6 non–glaucomatous controls. In contrast, VGLUT1 levels were unchanged. These results were confirmed using quantitative real–time PCR. Decreased VGLUT2 expression levels correlated with histological loss of RGC in aged, glaucomatous DBA2/J mice.
DBA2/J mice develop chronic progressive glaucoma associated with pigment dispersion. In a genome–wide differential gene expression study of the retinas of DBA2/J mice, VGLUT2 was discovered to be selectively down–regulated. This down–regulation of VGLUT2 is associated with histological loss of retinal ganglion cells and decreased electrical signaling activity as measured by electroretinography. VGLUT2 has been suggested to be expressed only in RGC in the retina. VGLUT2, but not VGLUT1, expression is associated with the pathophysiology of DBA2/J glaucoma.
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