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12/21/13 Gamma-Synuclein Is a Marker for Retinal Ganglion Cell Loss in Glaucoma -- Pomerleau et al.

46 (5): 5347 -- ARVO Meeting Abstracts


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Author: Keyword(s):
Year: Vol: Page:
Invest Ophthalmol Vis Sci 2005;46: E-Abstract 5347.
2005 ARVO
5347B550
GammaSynuclein Is a Marker for
Retinal Ganglion Cell Loss in Glaucoma
D.L. Pomerleau, M.S. Pezda, M. Tapia, A.S. Hackam and
R.K. Lee
Bascom Palmer Eye Institute, U. of Miami School of Medicine, Miami, FL
Commercial Relationships: D.L. Pomerleau, None; M.S. Pezda,
None; M. Tapia, None; A.S. Hackam, None; R.K. Lee, Pfizer F,
R.
Support: Pfizer Glaucoma Fellows Research Grant
Abstract
Purpose: Identification of molecules specifically downregulated

in the retina of glaucomatous mice. DBA2/J
mice develop chronic,

progressive glaucoma. In order to determine molecular pathways

involved in the
development of glaucoma, differential gene expression

analysis was used to identify genetic markers associated
with

the pathogenesis of glaucoma in a mouse model.
Methods: Pooled whole retinas from young, nonglaucomatous

(younger than 3 months of age) and from aged,
glaucomatous (12

months and older) DBA2/J mice were homogenized and total RNA

was extracted using Trizol
and purified with Qiagen RNeasy separation

columns. First strand cDNA was synthesized and hybridized to
Affymetrix GeneChip Mouse Genome 430 2.0 gene expression microarrays.

Retina cDNA was also used for
realtime PCR with alpha,

beta, and gammasynuclein and thy1 primers

to quantitatively confirm the
microarray gene expression data.

In addition, immunohistochemistry using gammasynuclein

antibodies was used
to determine protein expression levels.
Results: Gene expression microarray data was analyzed with Affymetrix

Microarray Suite 5.0 software and
gammasynuclein was

identified as one of the top fifteen most highly downregulated

genes expressed in aged,
glaucomatous DBA2/J retinas compared

to young, nonglaucomatous DBA2/J retinas. This finding

correlated
with the histological loss of retinal ganglion cells

(RGC) in the glaucomatous retinas. Gammasynuclein down
12/21/13 Gamma-Synuclein Is a Marker for Retinal Ganglion Cell Loss in Glaucoma -- Pomerleau et al. 46 (5): 5347 -- ARVO Meeting Abstracts
abstracts.iovs.org/cgi/content/abstract/46/5/5347 2/2
regulation

was confirmed on the transcriptional level using realtime

PCR and on the translational level by
immunohistochemistry,

which also localized expression of gammasynuclein in

the retina to RGC. A direct
relationship was found between gammasynuclein

and thy1 expression levels by realtime PCR.
Conclusions: In a genome wide screen of genes expressed in the

mouse retina, we found aged DBA2/J retinas
from 12 to 17 month

old mice with glaucomatous loss of RGC have significantly decreased

levels of gamma
synuclein expression that correlate with

age and severity of RGC loss. The progressive loss of RGC in

glaucoma
also correlated with loss of RGC marker thy1

expression. The finding that thy1 levels are directly

correlated to
gammasynuclein levels suggest that gammasynuclein

can be used a marker for RGC loss, since both molecules
are

selectively expressed in RGC. Gammasynuclein has been

suggested to be an antiapoptotic molecule. The
association

of decreased gammasynuclein expression levels with decreased

numbers of RGC suggest
expression of gammasynuclein may

be neuroprotective.
Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) retinal degenerations: hereditary
2005, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any part of this abstract, contact the ARVO Office at
arvo@arvo.org.
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