| Pharmacological Enhancement of ex vivo Gene Therapy Neuroprotection in a Rodent Model of Retinal Degeneration. | |
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MedLine Citation:
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PMID: 21691141 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims: We have previously shown the benefits of cell-based delivery of neuroprotection in a rodent model of retinitis pigmentosa (RP). In order to maximise the effectiveness of this approach, we hypothesised that this could be augmented by combination with an aminoglycoside known to limit the abnormal RNA translation seen in this model. Methods: A rhodopsin TgN S334ter-4 rat model of RP underwent daily subcutaneous injection of 12.5 μg/g gentamicin from postnatal day 5 (P5). At P21, selected rats also underwent intravitreal injection of cells genetically engineered to oversecrete glial cell-derived neurotrophic factor. Histological imaging was undertaken to evaluate photoreceptor survival at P70 and compared with images from untreated TgN S334ter-4 rats and control Sprague-Dawley rats. Results: Statistically significant (p < 0.05) improvements in outer retinal indices were seen with this combination strategy when compared with results in rats treated with individual therapies alone. This improvement was most apparent in the peripheral retina, where the greatest degeneration was observed. Conclusions: We have shown that the combination of neuroprotection plus aminoglycoside read-through in an animal model of retinal degeneration improved the histological appearance of the retina such that it was statistically indistinguishable from unaffected controls. Further functional and longitudinal studies of this approach are warranted. |
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Authors:
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Kevin Gregory-Evans; Kelvin Po; Francis Chang; Cheryl Y Gregory-Evans |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-21 |
Journal Detail:
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Title: Ophthalmic research Volume: 47 ISSN: 1423-0259 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0267442 Medline TA: Ophthalmic Res Country: - |
Other Details:
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Languages: ENG Pagination: 32-38 Citation Subset: - |
Copyright Information:
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Copyright © 2011 S. Karger AG, Basel. |
Affiliation:
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Department of Ophthalmology and Visual Science, Faculty of Medicine, University of British Columbia, Vancouver, B.C., Canada. |
Export Citation:
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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