Potential Synergistic Protection of Retinal Ganglion Cells from Axotomy-Induced Apoptosis by Adenoviral Administration of Glial Cell Line-Derived Neurotrophic Factor and X-Chromosome-Linked Inhibitor of Apoptosis

Guido Straten; Christian Schmeer; Alexandra Kretz; Ellen Gerhardt; Sebastian Kügler; Jörg B. Schulz; Claude Gravel; Mathias Bähr; Stefan Isenmann

Neurobiology of Disease (Oct 2002)

Potential Synergistic Protection of Retinal Ganglion Cells from Axotomy-Induced Apoptosis by Adenoviral Administration of Glial Cell Line-Derived Neurotrophic Factor and X-Chromosome-Linked Inhibitor of Apoptosis

Guido Straten,
Christian Schmeer,
Alexandra Kretz,
Ellen Gerhardt,
Sebastian Kügler,
Jörg B. Schulz,
Claude Gravel,
Mathias Bähr,
Stefan Isenmann

Affiliations

Guido Straten: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Christian Schmeer: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Alexandra Kretz: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Ellen Gerhardt: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Sebastian Kügler: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Jörg B. Schulz: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Claude Gravel: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Mathias Bähr: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada
Stefan Isenmann: Neuroregeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Neurodegeneration Laboratory, Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany; Laboratorio de Neuroquı́mica, Instituto Venezolano de Investigaciones Cientificas, 1020A, Caracas, Venezuela; Department of Neurology, University of Göttingen, Göttingen, Germany; Centre de Recherche, Université Laval Robert-Giffard, Beauport, Québec, Canada

Journal volume & issue: Vol. 11, no. 1
pp. 123 – 133

Abstract

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Following transection of the optic nerve (ON) in the adult rat, retinal ganglion cells (RGCs) undergo degeneration, and within 14 days 85% of axotomized RGCs die by apoptosis. Adenoviral delivery of the mammalian caspase inhibitor X-chromosome-linked inhibitor of apoptosis (Ad.XIAP) to the ON stump leads to expression exclusively in RGCs and rescues 18.9% of the RGCs that would degenerate without treatment. Following adenoviral vector injection into the vitreous body, bioactive glial cell line-derived neurotrophic factor (Ad.GDNF) is expressed in the retina and secreted to rescue 22.8% of lesioned RGCs. Here we report that coadministration of Ad.XIAP retrogradely directed to RGCs and intravitreal Ad.GDNF acts synergistically to protect axotomized RGCs. Combination treatment rescued 47.3% of RGCs that would undergo apoptosis without any treatment as opposed to 37.4% that would be expected if the two treatments acted independently. While without treatment only 15% of axotomized RGCs would survive, combination treatment resulted in survival of 55.4% of the total RGC population. These findings underline the neuroprotective potential of synergistic effects of a combination of different treatment strategies.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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