Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.

We have recently demonstrated the characterization of human tyrosinase TCR bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune vitiligo and retinal dysfunction. The purpose of current study was to determine the role of T cells and IFN-γ in retina dysfunction and retinal gang...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shahid Husain, Yasir Abdul, Christine Webster, Shilpak Chatterjee, Pravin Kesarwani, Shikhar Mehrotra
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0eff5e21fe5d4b199fdfcd7653463b66
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0eff5e21fe5d4b199fdfcd7653463b66
record_format	dspace
spelling	oai:doaj.org-article:0eff5e21fe5d4b199fdfcd7653463b662021-11-18T08:30:32ZInterferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.1932-620310.1371/journal.pone.0089392https://doaj.org/article/0eff5e21fe5d4b199fdfcd7653463b662014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586745/?tool=EBIhttps://doaj.org/toc/1932-6203We have recently demonstrated the characterization of human tyrosinase TCR bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune vitiligo and retinal dysfunction. The purpose of current study was to determine the role of T cells and IFN-γ in retina dysfunction and retinal ganglion cell (RGC) death using this model. RGC function was measured by pattern electroretinograms (ERGs) in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Expression of CD3, IFN-γ, GFAP, and caspases was measured by immunohistochemistry and Western blotting. All functional and structural changes were measured in 12-month-old h3T-A2 mice and compared with age-matched HLA-A2 wild-type mice. Both pattern-ERGs (42%, p = 0.03) and RGC numbers (37%, p = 0.0001) were reduced in h3T-A2 mice when compared with wild-type mice. The level of CD3 expression was increased in h3T-A2 mice (h3T-A2: 174 ± 27% vs. HLA-A2: 100%; p = 0.04). The levels of effector cytokine IFN-γ were also increased significantly in h3T-A2 mice (h3T-A2: 189 ± 11% vs. HLA-A2: 100%; p = 0.023). Both CD3 and IFN-γ immunostaining were increased in nerve fiber (NF) and RGC layers of h3T-A2 mice. In addition, we have seen a robust increase in GFAP staining in h3T-A2 mice (mainly localized to NF layer), which was substantially reduced in IFN-γ ((-/-)) knockout h3T-A2 mice. We also have seen an up-regulation of caspase-3 and -9 in h3T-A2 mice. Based on our data we conclude that h3T-A2 transgenic mice exhibit visual defects that are mostly associated with the inner retinal layers and RGC function. This novel h3T-A2 transgenic mouse model provides opportunity to understand RGC pathology and test neuroprotective strategies to rescue RGCs.Shahid HusainYasir AbdulChristine WebsterShilpak ChatterjeePravin KesarwaniShikhar MehrotraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89392 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shahid Husain Yasir Abdul Christine Webster Shilpak Chatterjee Pravin Kesarwani Shikhar Mehrotra Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.
description	We have recently demonstrated the characterization of human tyrosinase TCR bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune vitiligo and retinal dysfunction. The purpose of current study was to determine the role of T cells and IFN-γ in retina dysfunction and retinal ganglion cell (RGC) death using this model. RGC function was measured by pattern electroretinograms (ERGs) in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Expression of CD3, IFN-γ, GFAP, and caspases was measured by immunohistochemistry and Western blotting. All functional and structural changes were measured in 12-month-old h3T-A2 mice and compared with age-matched HLA-A2 wild-type mice. Both pattern-ERGs (42%, p = 0.03) and RGC numbers (37%, p = 0.0001) were reduced in h3T-A2 mice when compared with wild-type mice. The level of CD3 expression was increased in h3T-A2 mice (h3T-A2: 174 ± 27% vs. HLA-A2: 100%; p = 0.04). The levels of effector cytokine IFN-γ were also increased significantly in h3T-A2 mice (h3T-A2: 189 ± 11% vs. HLA-A2: 100%; p = 0.023). Both CD3 and IFN-γ immunostaining were increased in nerve fiber (NF) and RGC layers of h3T-A2 mice. In addition, we have seen a robust increase in GFAP staining in h3T-A2 mice (mainly localized to NF layer), which was substantially reduced in IFN-γ ((-/-)) knockout h3T-A2 mice. We also have seen an up-regulation of caspase-3 and -9 in h3T-A2 mice. Based on our data we conclude that h3T-A2 transgenic mice exhibit visual defects that are mostly associated with the inner retinal layers and RGC function. This novel h3T-A2 transgenic mouse model provides opportunity to understand RGC pathology and test neuroprotective strategies to rescue RGCs.
format	article
author	Shahid Husain Yasir Abdul Christine Webster Shilpak Chatterjee Pravin Kesarwani Shikhar Mehrotra
author_facet	Shahid Husain Yasir Abdul Christine Webster Shilpak Chatterjee Pravin Kesarwani Shikhar Mehrotra
author_sort	Shahid Husain
title	Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.
title_short	Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.
title_full	Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.
title_fullStr	Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.
title_full_unstemmed	Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.
title_sort	interferon-gamma (ifn-γ)-mediated retinal ganglion cell death in human tyrosinase t cell receptor transgenic mouse.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/0eff5e21fe5d4b199fdfcd7653463b66
work_keys_str_mv	AT shahidhusain interferongammaifngmediatedretinalganglioncelldeathinhumantyrosinasetcellreceptortransgenicmouse AT yasirabdul interferongammaifngmediatedretinalganglioncelldeathinhumantyrosinasetcellreceptortransgenicmouse AT christinewebster interferongammaifngmediatedretinalganglioncelldeathinhumantyrosinasetcellreceptortransgenicmouse AT shilpakchatterjee interferongammaifngmediatedretinalganglioncelldeathinhumantyrosinasetcellreceptortransgenicmouse AT pravinkesarwani interferongammaifngmediatedretinalganglioncelldeathinhumantyrosinasetcellreceptortransgenicmouse AT shikharmehrotra interferongammaifngmediatedretinalganglioncelldeathinhumantyrosinasetcellreceptortransgenicmouse
_version_	1718421664751943680

Interferon-gamma (IFN-γ)-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.

Ejemplares similares