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γ-Synuclein as a marker of retinal ganglion cells

PURPOSE: Previous studies have described γ-synuclein as a protein highly expressed in retinal ganglion cells (RGCs), and a loss of RGCs correlates with a downregulation of γ-synuclein gene expression in glaucoma. Here we asked whether γ-synuclein expression in the retina can be considered a specific...

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Autores principales: Surgucheva, Irina, Weisman, Alejandra D., Goldberg, Jeffrey L., Shnyra, Alexander, Surguchov, Andrei
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2008
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518532/
https://www.ncbi.nlm.nih.gov/pubmed/18728752
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author Surgucheva, Irina
Weisman, Alejandra D.
Goldberg, Jeffrey L.
Shnyra, Alexander
Surguchov, Andrei
author_facet Surgucheva, Irina
Weisman, Alejandra D.
Goldberg, Jeffrey L.
Shnyra, Alexander
Surguchov, Andrei
author_sort Surgucheva, Irina
collection PubMed
description PURPOSE: Previous studies have described γ-synuclein as a protein highly expressed in retinal ganglion cells (RGCs), and a loss of RGCs correlates with a downregulation of γ-synuclein gene expression in glaucoma. Here we asked whether γ-synuclein expression in the retina can be considered a specific marker of RGCs. METHODS: γ-Synuclein expression was examined with immunohistochemistry in retinal sections from normal and glaucomatous human eyes. Primary cultures of RGCs from Sprague-Dawley rats purified by sequential immunopanning using a monoclonal antibody to Thy1–1, cultures of A7 immortalized optic nerve astrocytes from newborn rats, and the immortalized RGC-5 cell line were studied using immunofluorescence and quantitative RT–PCR. RESULTS: γ-Synuclein was highly expressed in RGCs in the human retina and was localized in cytoplasm adjacent to the RGC nuclear marker, Brn-3a. Axons of RGCs were immunopositive for γ-synuclein in the nerve fiber layer (NFL), the lamina cribrosa and the retrobulbar optic nerve. In the optic nerve of glaucoma patients, axon swellings were likewise immunopositive, whereas in the retina of patients with retinoblastoma, NFL staining appeared reduced. In primary rat RGCs and in immortalized RGC-5 cultures, γ-synuclein was localized predominantly in the perinuclear area and in cell processes. Among rat retinal cells in culture, all Brn-3a positive cells were stained with a γ-synuclein antibody; rare γ-synuclein-positive cells were not stained by the Brn-3a antibody. CONCLUSIONS: γ-Synuclein is selectively and abundantly expressed in human RGCs in vivo, primary rat RGCs in vitro, and immortalized RGC-5 cells. In pathology, γ-synuclein abundance may vary between RGC somas and axons. Coincident Brn-3a and γ-synuclein expression suggests that strong γ-synuclein expression can be considered a marker of RGCs. Future translational approaches might include using a γ-synuclein promoter for the specific delivery of siRNA or therapeutic proteins to RGCs.
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spelling pubmed-25185322008-08-26 γ-Synuclein as a marker of retinal ganglion cells Surgucheva, Irina Weisman, Alejandra D. Goldberg, Jeffrey L. Shnyra, Alexander Surguchov, Andrei Mol Vis Research Article PURPOSE: Previous studies have described γ-synuclein as a protein highly expressed in retinal ganglion cells (RGCs), and a loss of RGCs correlates with a downregulation of γ-synuclein gene expression in glaucoma. Here we asked whether γ-synuclein expression in the retina can be considered a specific marker of RGCs. METHODS: γ-Synuclein expression was examined with immunohistochemistry in retinal sections from normal and glaucomatous human eyes. Primary cultures of RGCs from Sprague-Dawley rats purified by sequential immunopanning using a monoclonal antibody to Thy1–1, cultures of A7 immortalized optic nerve astrocytes from newborn rats, and the immortalized RGC-5 cell line were studied using immunofluorescence and quantitative RT–PCR. RESULTS: γ-Synuclein was highly expressed in RGCs in the human retina and was localized in cytoplasm adjacent to the RGC nuclear marker, Brn-3a. Axons of RGCs were immunopositive for γ-synuclein in the nerve fiber layer (NFL), the lamina cribrosa and the retrobulbar optic nerve. In the optic nerve of glaucoma patients, axon swellings were likewise immunopositive, whereas in the retina of patients with retinoblastoma, NFL staining appeared reduced. In primary rat RGCs and in immortalized RGC-5 cultures, γ-synuclein was localized predominantly in the perinuclear area and in cell processes. Among rat retinal cells in culture, all Brn-3a positive cells were stained with a γ-synuclein antibody; rare γ-synuclein-positive cells were not stained by the Brn-3a antibody. CONCLUSIONS: γ-Synuclein is selectively and abundantly expressed in human RGCs in vivo, primary rat RGCs in vitro, and immortalized RGC-5 cells. In pathology, γ-synuclein abundance may vary between RGC somas and axons. Coincident Brn-3a and γ-synuclein expression suggests that strong γ-synuclein expression can be considered a marker of RGCs. Future translational approaches might include using a γ-synuclein promoter for the specific delivery of siRNA or therapeutic proteins to RGCs. Molecular Vision 2008-08-22 /pmc/articles/PMC2518532/ /pubmed/18728752 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Surgucheva, Irina
Weisman, Alejandra D.
Goldberg, Jeffrey L.
Shnyra, Alexander
Surguchov, Andrei
γ-Synuclein as a marker of retinal ganglion cells
title γ-Synuclein as a marker of retinal ganglion cells
title_full γ-Synuclein as a marker of retinal ganglion cells
title_fullStr γ-Synuclein as a marker of retinal ganglion cells
title_full_unstemmed γ-Synuclein as a marker of retinal ganglion cells
title_short γ-Synuclein as a marker of retinal ganglion cells
title_sort γ-synuclein as a marker of retinal ganglion cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518532/
https://www.ncbi.nlm.nih.gov/pubmed/18728752
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