Award details

Genetic modification of retinal ganglion cells to overcome growth inhibition and cell death and to increase axonal regeneration

Reference	BB/C502973/1
Principal Investigator / Supervisor	Dr Gregor Campbell
Co-Investigators / Co-Supervisors	Professor Patrick Anderson
Institution	University College London
Department	Cell and Developmental Biology
Funding type	Research
Value (£)	137,192
Status	Completed
Type	Research Grant
Start date	01/11/2004
End date	30/11/2007
Duration	37 months

Abstract

Success in repairing the damaged CNS in adult mammals is likely to depend on a combination of treatments designed to promote survival of axotomised neurons, to enhance regrowth of their axons, to block effects of growth inhibitory molecules and to reduce scar formation. In this study we shall employ multiple approaches to enhance the regeneration of adult rat retinal ganglion cell (RGC) axons within the injured optic nerve. We shall prime RGCs with neurotrophic factors delivered by retrograde transport of viral vectors before crushing the optic nerve. We shall inactivate RhoA, a small GTPase at the centre of signalling pathways leading to inhibition of axon growth. Viral vectors will then deliver dominant negative RhoA to RGCs to block these pathways. Nogo, MAG, OMgp ephrin-A3, and proteoglycans have all been shown to inhibit RGC axon growth and they all exert their inhibitory action via RhoA. Regenerating axons will be anterogradely labelled following intravitreal injections of tracer. To further boost the regenerative response of RGCs, in some experiments we will combine these treatments with a lens lesion which others have shown to lead to regeneration of some RGC axons. We anticipate that this combination of treatments will lead to robust regeneration of RGC axons through the optic nerve to their targets in the brain.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	LINK: Animal Sciences Committee (ASL) [1996-2004]
Funding Scheme	X – not Funded via a specific Funding Scheme

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search