title: Expression of the diabetes risk gene wolframin (WFS1) in the human retina.
abstract: 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.
authors.affiliation: Charles E. Schmidt College of Biomedical Science, Florida Atlantic University, 777 Glades Road, P.O. Box 3091, Boca Raton, FL 33431, USA. schmidtk@fau.edu
authors.forename: Rainald
authors.initials: R
authors.lastname: Schmidt-Kastner
authors.forename: Pawel
authors.initials: P
authors.lastname: Kreczmanski
authors.forename: Markus
authors.initials: M
authors.lastname: Preising
authors.forename: Roselie
authors.initials: R
authors.lastname: Diederen
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmitz
authors.forename: Danielle
authors.initials: D
authors.lastname: Reis
authors.forename: Janet
authors.initials: J
authors.lastname: Blanks
authors.forename: C Kathleen
authors.initials: CK
authors.lastname: Dorey
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012160:Retina / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein