Expression of the diabetes risk gene wolframin (WFS1) in the human retina

被引:32
作者
Schmidt-Kastner, Rainald [1 ]
Kreczmanski, Pawel [4 ]
Preising, Markus [5 ,6 ]
Diederen, Roselie [4 ]
Schmitz, Christoph [4 ]
Reis, Danielle [1 ,2 ]
Blanks, Janet [2 ]
Dorey, C. Kathleen [1 ,2 ,3 ]
机构
[1] Florida Atlantic Univ, Charles E Schmidt Coll Biomed Sci, Boca Raton, FL 33431 USA
[2] Florida Atlantic Univ, Charles E Schmidt Coll Sci, Boca Raton, FL 33431 USA
[3] Florida Atlantic Univ, Christine E Lynn Coll Nursing, Boca Raton, FL 33431 USA
[4] Maastricht Univ, Div Neurosci, Sch Mental Hlth & Neurosci, Maastricht, Netherlands
[5] Univ Giessen, Univ Giessen Klinikum, Dept Ophthalmol, D-35390 Giessen, Germany
[6] Marburg GmbH, Marburg, Germany
关键词
retina; diabetes; optic nerve; RPE; neurodegeneration; immunohistochemistry; ENDOPLASMIC-RETICULUM STRESS; PANCREATIC BETA-CELLS; UNFOLDED PROTEIN RESPONSE; OPTIC ATROPHY; TRANSMEMBRANE PROTEIN; DEAFNESS DIDMOAD; GANGLION-CELLS; HUMAN MACULA; ER STRESS; MICE;
D O I
10.1016/j.exer.2009.05.007
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Wolfram syndrome 1 (WFS1, OMIM 222300), a rare genetic disorder characterized by optic nerve atrophy, deafness, diabetes insipidus and diabetes mellitus, is caused by mutations of WFS1, encoding WFS1/wolframin. Non-syndromic WFS1 variants are associated with the risk of diabetes mellitus due to altered function of wolframin in pancreatic islet cells, expanding the importance of wolframin. This study extends a previous report for the monkey retina, using immunohistochemistry to localize wolframin on cryostat and paraffin sections of human retina. In addition, the human retinal pigment epithelial (RPE) cell line termed ARPE-19 and retinas from both pigmented and albino mice were studied to assess wolframin localization. In the human retina, wolframin was expressed in retinal ganglion cells, optic axons and the proximal optic nerve. Wolframin expression in the human retinal pigment epithelium (RPE) was confirmed with intense cytoplasmic labeling in ARPE-19 cells. Strong labeling of the RPE was also found in the albino mouse retina. Cryostat sections of the mouse retina showed a more extended pattern of wolframin labeling, including the inner nuclear layer (INL) and photoreceptor inner segments, confirming the recent report of Kawano et al. [Kawano, J., Tanizawa, Y., Shinoda, K., 2008. Wolfram syndrome 1 (Wfs1) gene expression in the normal mouse visual system. J. Comp. Neurol. 510, 1-23]. Absence of these cells in the human specimens despite the use of human-specific antibodies to wolframin may be related to delayed fixation. Loss of wolframin function in RGCs and the unmyelinated portion of retinal axons could explain optic nerve atrophy in Wolfram Syndrome 1. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:568 / 574
页数:7
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