The role of axonal retrograde transport in the pathogenesis of glaucoma

• Applicant: Dr. Christian Noack
• Subject Area: Ophthalmology
• Term: from 2007 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 35634273

Although glaucoma is a disease with an estimated prevalence of about 67 million, little is known about the pathological mechanisms leading to retinal ganglion cell death. Among the known risk factors, elevated intraocular pressure and microvascular insufficency are thought to be particularly important. However, the pathogenic chain linking these risk factors to axonal degeneration and apoptosis remains elusive. There is rising evidence that the retrograde axonal transport of neurotrophic factors (mainly brain derived neurotrophic factor – BDNF) is impaired in glaucoma. Interruption of neurotrophic signalling from superior colliculus to retinal ganglion cell (RGC) somata may contribute to RGC degeneration.The proposed work is intended to investigate the alterations to the retrograde transport system with a focus on the Dynein motor complex in a rat chronic glaucoma model. Using techniques like immunostaining, quantitative Western blotting and rtPCR we will analyse mRNA levels as well as distribution and posttranslational modification of proteins belonging to the axonal transport system.Furthermore, we will monitor in vivo the retrograde axonal transport of fluorescently labelled BDNF injected to the superior colliculus. This would be the first direct test to the hypothesis of neurotrophin deprivation under glaucomatous conditions. Depending on these results we would further investigate the correlation between impaired retrograde axonal transport and apoptosis.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Keith Martin