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Third-party-funded project

Title:
The role of growth factors and neurotrophic factors as signaling molecules for the interaction between mesenchyme, vascular system and sensory epithelium of the cochlea

Project management at the University of Würzburg:

Participating scientists:

Abstract:
Vascular and autoimmune cochlear disregulations are considered to be the main reasons for inner ear diseases affecting about 15 million people in Germany. Because of missing causal therapy concepts, further investigations are necessary to clarify the underlying molecular mechanisms responsible for inner ear pathology.
The main intention of the project described here is to investigate changes in the cochlear capillary network and the resulting damages of inner ear tissues. In this context, different growth factors such as members of the FGF and neurotrophin family are of interest since they act as mitogens for inner ear cells as well as stimuli for different aspects of vasculogenesis. These factors may play a role in signal transduction between endothelial, mesenchymal, or sensorineural cells of the cochlea.
In the center of the present project are the generation and investigations of different mouse mutants in which e.g. the neurotrophin receptor p75, the IGF-1 receptor, and the FGF receptor 2 expressed by endothelial cells will be inactivated. In case of the IGF-1 receptor and the FGF receptor 2 cell type specific inactivation will be performed via Cre recombination in mesenchymal, endothelial, and cochlear hair cells.
Adenoviral gene transfer will be used as a mediatior for cochlear overexpression of the growth factors mentioned above. The expected neurotophic effects will be determined by elektrophysiology and histology with regard to protection and regeneration of inner ear tissues.
Damages of mammalian cochlear sensory cells are usually irreversible. The comparison of the expression patterns of these factors during the cochlear differentiation in mice and chicken as well as the analysis of a possible regeneration after aminoglycosid treatment may uncover differences between mammalian and bird inner ear since hair cell regeneration is possible throughout life in the latter.
We expect to find new aspects of growth factor involvement in signal transduction between endothelial, mesenchymal and cochlear hair cells taking part in preservation and regeneration processes in inner ear cells from this project. Thus, these investigations may lead to fundamental new aspects for therapeutic strategies in the treatment of common inner ear deseases such as acute hearing loss, tinnitus and chronic cochlear hearing loss.

Projekt period: from 05.2002 to 04.2004

Funding institution:
Landeshaushalt Wissenschaftsministerium
Bund