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 1/2 This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pomerleau, D.L. Articles by Lee, R.K. Search for Related Content PubMed Articles by Pomerleau, D.L. Articles by Lee, R.K. HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH QUICK SEARCH: [advanced] Go 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. HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH