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Vol. 47, No. 1, 2012
Issue release date: December 2011
Section title: Original Paper
Ophthalmic Res 2012;47:32–38
(DOI:10.1159/000325730)

Pharmacological Enhancement of ex vivo Gene Therapy Neuroprotection in a Rodent Model of Retinal Degeneration

Gregory-Evans K.a, b · Po K.a · Chang F.b · Gregory-Evans C.Y.a, b
aDepartment of Ophthalmology and Visual Science, Faculty of Medicine, University of British Columbia, Vancouver, B.C., Canada; bDepartment of Clinical Neuroscience, Faculty of Medicine, Imperial College London, London, UK

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/29/2010
Accepted: 2/11/2011
Published online: 6/21/2011
Issue release date: December 2011

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: http://www.karger.com/ORE

Abstract

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.


  

Author Contacts

Kevin Gregory-Evans
Department of Ophthalmology and Visual Sciences, University of British Columbia
Eye Care Centre, 2550 Willow Street
Vancouver, BC V5Z3N9 (Canada)
Tel. +1 604 671 0419, E-Mail kge30@interchange.ubc.ca

  

Article Information

Received: July 29, 2010
Accepted after revision: February 11, 2011
Published online: June 21, 2011
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 1, Number of References : 53

  

Publication Details

Ophthalmic Research (Journal for Research in Experimental and Clinical Ophthalmology)

Vol. 47, No. 1, Year 2012 (Cover Date: December 2011)

Journal Editor: Pleyer U. (Berlin)
ISSN: 0030-3747 (Print), eISSN: 1423-0259 (Online)

For additional information: http://www.karger.com/ORE


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/29/2010
Accepted: 2/11/2011
Published online: 6/21/2011
Issue release date: December 2011

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: http://www.karger.com/ORE


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