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R. G. Schmidt-Kastner, P. Kreczmanski, H. Yamamoto, M. Preising, R. Diederen, C. J. Dougherty, J.-M. Parel, C. Schmitz, J. Blanks, C. K. Dorey; The Diabetes Risk Gene Wolframin (WFS1) Is Expressed in Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):166.
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© ARVO (1962-2015); The Authors (2016-present)
The study of rare monogenic disorders can generate novel insight into common disorders such as diabetes. Mutations of WFS1 (wolframin) cause recessive Wolfram syndrome, characterized by diabetes, optic atrophy and deafness. Wolframin is expressed in pancreatic islet cells, and common WFS1 variants have been associated with the risk of type 2 diabetes. We reported expression of wolframin in monkey retinal ganglion cells (RGCs; Yamamoto et al., 2006). This study describes expression of wolframin in human and rat retinas. Additional risk genes for diabetes were searched for expression in the retina in silico.
Immunohistochemistry was performed on retinal sections obtained from human donor eyes (with no prior history of diabetes) using an affinity purified polyclonal antibody against the N-terminus of human wolframin (Yamamoto et al., 2006). To analyze expression in RPE, sections of albino rats and (human) ARPE-19 cells were also studied. A list of diabetes risk genes was compiled from current reviews. Retinal mRNA expression data of diabetes risk genes were probed in EyeBank using WFS1 as a reference. Further evidence for retinal expression was retrieved from PubMed.
Wolframin was localized in human and rat RGCs. The RPE of albino rats and ARPE-19 cells expressed wolframin. Diabetes risk genes listed in EyeBank for expression in the retina and reported in specific studies on the retina included NEUROD1, FTO and ABCC8/SUR1.
Diabetic retinopathy is commonly interpreted as the consequence of systemic hyperglycemia. Primary retinal dysfunction in diabetes has been also proposed. Expression of wolframin in the human retina, documented here at the protein level, and retinal expression of three additional diabetes risk genes provide a novel, genetic aspect for primary retinal dysfunction in diabetic retinopathy.
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