Journal article
Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signaling
A Osborne, TZ Khatib, L Songra, AC Barber, K Hall, GYX Kong, PS Widdowson, KR Martin
Cell Death and Disease | NATURE PUBLISHING GROUP | Published : 2018
Abstract
Previous studies have demonstrated that intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury. BDNF gene therapy can improve RGC survival in experimental models of glaucoma, the leading cause of irreversible blindness worldwide. However, the therapeutic efficacy of BDNF supplementation alone is time limited at least in part due to BDNF receptor downregulation. Tropomyosin-related receptor kinase-B (TrkB) downregulation has been reported in many neurological diseases including glaucoma, potentially limiting the effect of sustained or repeated BDNF delivery..
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Awarded by Wellcome Trust
Funding Acknowledgements
The authors acknowledge a Wellcome Trust Pathfinder Award which partially supported this work. Special thanks to Susan Wilson (Histochemistry Research Unit, Southampton General Hospital) and Robert Adalbert (John van Geest Centre for Brain Repair, University of Cambridge) for assistance with optic nerve sectioning and processing. Thank you also to Nicolas Belforte (Department of Neurosciences, University of Montreal) for advice on quantifying fluorescence within individual RGCs. This work was supported by, the Midven Rainbow Seed Fund, Quethera Ltd, University of Cambridge Enterprise, the HB Allen Charitable Trust, and the Cambridge Eye Trust.