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Repair of damaged mammalian visual pathways

Objective

Our primary objectives are to study injured retinal ganglion cells (RGCs) and how to promote successful repair after damage, with the ultimate aims of restoring lost visual function and providing a model system in which to define strategies for recovery of damaged circuitry in the brain.

Our primary objectives are to develop a research programme to study injured retinal ganglion cells (RGCs) and how to promote successful repair after damage, with the ultimate aim of restoring lost visual function. Axons of RGCs form the optic nerve along which visual information passes from the eye to the brain and one approach centres on the effects of optic nerve damage on RGCs, using peripheral nerve grafting and growth factor replacement strategies to stimulate axon regeneration. The second approach focuses on replacing the damaged system by transplanting a new retina, which forms connections with the host brain. These two approaches have been the major research areas of several of the participating groups for many years. The present proposal broadens that work by examining biophysical and molecular correlates of injury and repair and attempting to improve the efficiency of the repair process. Functional assessment of the repair process is a key element in the project since the goal is to define a strategy that will lead to maximal recovery of vision.

We will pursue the following research tasks:
1) Ganglion cell death and its prevention. The goal here is to understand the cause and correlates of this process and to arrest it so that RGCs are able to respond to axon growth-promoting treatments;
2) Promotion of out growth. The main purpose is to define the molecular correlate of successful regeneration and how expression of these molecules can be modulated to promote axonal regeneration. Emphasis will be directed at defining necessary substrates for axonal outgrowth and how growth factors and their receptors influence this process;
3) Circuit reconstruction. Here we plan to examine how successfully regenerated axons or those from transplanted retinae are able to reconstruct the circuits of the intact visual pathway. Most important is to develop a system whereby an illals can 'see' rather than simply respond reflexively to visual signals relayed by the new pathways;
4) Functional assessment. Central to any repair strategy is assessment of impact on function. A regenerated pathway is no use if it relays nonsense information. The interaction between those preparing the regeneration strategy and those who can evaluate functional impact is crucial.

The expected outcome of this work is the development of a protocol foroptimal recovery of the primary visual pathway after injury; this informationwill also be of value for promoting repair of non-visual brain regions. These objectives/outcomes could not be achieved by means other than the interactive approach of a coordinated programme.

KEYWORDS: Axon Regeneration; Brain repair; Retinal ganglion cells; Optic nerve; Visual function; Transplantation; Schwann.

KEYWORDS(maxl0) cells, Trophic factors; Neuronal death; Adhesion02. 02

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Institute of Ophthalmology
Address
Bath Street
EC1V 9EL London
United Kingdom

Participants (6)

UNIVERSITY COLLEGE LONDON
United Kingdom
Address
Gower Street
London
UNIVERSITY OF MODENA AND REGGIO EMILIA
Italy
Address
Via G.campi 287
41100 Modena
UPPSALA UNIVERSITY
Sweden
Address
3,University Hospital
751 85 Uppsala
Universidad de Alcala de Henares
Spain
Address
Km 33,Carretera De Barcelona
28871 Madrid
Universidad de Murcia
Spain
Address

30100 Murcia
University of Sheffield
United Kingdom
Address
Western Bank
S10 2TN Sheffield