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Retinal Structure and Function in an Animal Model that Replicates the Biochemical Hallmarks of Desmosterolosis

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Abstract

Desmosterolosis is a rare, autosomal recessive, human disease characterized by multiple congenital anomalies in conjunction with grossly elevated levels of desmosterol and markedly reduced levels of cholesterol in all bodily tissues. Herein, we evaluated retinal sterol composition, histology, and electrophysiological function in an animal model that exhibited the biochemical features of desmosterolosis, produced by treating pregnant rats and their progeny with U18666A, an inhibitor of desmosterol reductase. Treated rats had cataracts, were substantially smaller, and had markedly high levels of desmosterol and profoundly low levels of cholesterol in their retinas and other tissues compared to age-matched controls. However, their retinas were histologically normal and electrophysiologically functional. These results suggest that desmosterol may be able to replace cholesterol in the retina, both structurally and functionally. These findings are discussed in the context of “sterol synergism.”

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Authors and Affiliations

  1. Saint Louis University Eye Institute and the Cell and Molecular Biology Graduate Program, Saint Louis University School of Medicine, St. Louis, MO

    Steven J. Fliesler

  2. Saint Louis University Eye Institute and the Cell and Molecular Biology Graduate Program, Saint Louis University School of Medicine, St. Louis, MO

    Michael J. Richards & Chi-yen Miller

  3. Research Service, Hines VA Hospital, Hines, IL

    Neal S. Peachey

  4. Departments of Neurology and Ophthalmology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL

    Neal S. Peachey

  5. Department of Biochemistry, Kirksville College of Osteopathic Medicine, Kirksville, MO

    Richard J. Cenedella

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  1. Steven J. Fliesler
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  4. Neal S. Peachey
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  5. Richard J. Cenedella
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Fliesler, S.J., Richards, M.J., Miller, Cy. et al. Retinal Structure and Function in an Animal Model that Replicates the Biochemical Hallmarks of Desmosterolosis. Neurochem Res 25, 685–694 (2000). https://doi.org/10.1023/A:1007519321917

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