Low cholesterol cues cataract development

Cataracts are a leading cause of blindness worldwide. Using a rat model of cataract formation, Masayuki Mori and researchers at Shinshu University Graduate School of Medicine in Japan have now found a link between cataracts and cholesterol.

The study, appearing online on January 26 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation reports that a primary genetic defect in cataractogenesis is combined mutation of the lanosterol synthase (Lss) and farnesyl diphosphate farnesyl transferase 1 (Fdft1) genes, both of which function in cholesterol biosynthesis. Cataractous rats with these 2 gene mutations demonstrated reduced cholesterol levels in the eye lens and cerebral cortex, compared to wild-type rats. The researchers also identified a problem with specialized cells of the eye lens, known as epithelial cells.

These cells, which require cholesterol for proper development, normally form a thin, single layer across the lens and are responsible for maintaining the transparency of the lens. In cataracts, these cells fail to mature normally, and Mori's group now shows that epithelial cells of cataractous rats with mutations in Lss and Fdft1 also mature abnormally, suggesting that the defect in cholesterol synthesis alters proliferation of these cells and contributes to the lens becoming opaque.

The results could have clinical impact in patients taking cholesterol–lowering medications or in individuals with inborn defects in cholesterol synthesis.

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TITLE: Lanosterol synthase mutations cause cholesterol deficiency–associated cataracts in the Shumiya cataract rat

AUTHOR CONTACT: Masayuki Mori
Shinshu University Graduate School of Medicine, Matsumoto, Japan
Phone: 81-263-37-2692; Fax: 81-263-37-3428; E-mail: masamori@sch.md.shinshu-u.ac.jp

View the PDF of this article at: https://www.the-jci.org/article.php?id=20797


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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