Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive human disease caused by mutations in the gene encoding 7-dehydrocholesterol (7DHC) reductase (DHCR7), resulting in abnormal accumulation of 7DHC and reduced levels of cholesterol in bodily tissues and fluids. A rat model of the disease has...
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| Format: | Article |
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MDPI AG
2018-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/10/2720 |
| _version_ | 1828514884733632512 |
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| author | Steven J. Fliesler Libin Xu |
| author_facet | Steven J. Fliesler Libin Xu |
| author_sort | Steven J. Fliesler |
| collection | DOAJ |
| description | Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive human disease caused by mutations in the gene encoding 7-dehydrocholesterol (7DHC) reductase (DHCR7), resulting in abnormal accumulation of 7DHC and reduced levels of cholesterol in bodily tissues and fluids. A rat model of the disease has been created by treating normal rats with the DHCR7 inhibitor, AY9944, which causes progressive, irreversible retinal degeneration. Herein, we review the features of this disease model and the evidence linking 7DHC-derived oxysterols to the pathobiology of the disease, with particular emphasis on the associated retinal degeneration. A recent study has shown that treating the rat model with cholesterol plus suitable antioxidants completely prevents the retinal degeneration. These findings are discussed with regard to their translational implications for developing an improved therapeutic intervention for SLOS over the current standard of care. |
| first_indexed | 2024-12-11T18:05:59Z |
| format | Article |
| id | doaj.art-bb80874c537d4c29973cb91a7c2450ce |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T18:05:59Z |
| publishDate | 2018-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bb80874c537d4c29973cb91a7c2450ce2022-12-22T00:55:44ZengMDPI AGMolecules1420-30492018-10-012310272010.3390/molecules23102720molecules23102720Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic InterventionSteven J. Fliesler0Libin Xu1Departments of Ophthalmology and Biochemistry and Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260, USADepartment of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA 98195, USASmith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive human disease caused by mutations in the gene encoding 7-dehydrocholesterol (7DHC) reductase (DHCR7), resulting in abnormal accumulation of 7DHC and reduced levels of cholesterol in bodily tissues and fluids. A rat model of the disease has been created by treating normal rats with the DHCR7 inhibitor, AY9944, which causes progressive, irreversible retinal degeneration. Herein, we review the features of this disease model and the evidence linking 7DHC-derived oxysterols to the pathobiology of the disease, with particular emphasis on the associated retinal degeneration. A recent study has shown that treating the rat model with cholesterol plus suitable antioxidants completely prevents the retinal degeneration. These findings are discussed with regard to their translational implications for developing an improved therapeutic intervention for SLOS over the current standard of care.http://www.mdpi.com/1420-3049/23/10/2720antioxidantcholesteroldegenerationoxysterolretinaSmith-Lemli-Opitz syndrome |
| spellingShingle | Steven J. Fliesler Libin Xu Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention Molecules antioxidant cholesterol degeneration oxysterol retina Smith-Lemli-Opitz syndrome |
| title | Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention |
| title_full | Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention |
| title_fullStr | Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention |
| title_full_unstemmed | Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention |
| title_short | Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention |
| title_sort | oxysterols and retinal degeneration in a rat model of smith lemli opitz syndrome implications for an improved therapeutic intervention |
| topic | antioxidant cholesterol degeneration oxysterol retina Smith-Lemli-Opitz syndrome |
| url | http://www.mdpi.com/1420-3049/23/10/2720 |
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