advertisement
Abstract #46763 Published in IGR 13-3
Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open angle glaucoma
Pasutto F; Matsumoto T; Mardin CY; Sticht H; Brandstatter JH; Michels-Rautenstrauss K; Weisschuh N; Gramer E; Ramdas WD; van Koolwijk LMEMedizinische Genetik 2010; 22: 87
Glaucoma, a main cause of blindness in the developed world, is characterized by progressive degeneration of retinal ganglion cells (RGCs) resulting in irreversible loss of vision. While members of the neuro-trophin gene family in various species are known to support the survival of numerous neuronal populations, including RGCs, it is less clear whether they are also required for survival and maintenance of adult neurons in humans. Here we report seven different heterozygous mutations in Neurotrophin-4 (NTF4) gene accounting for about 1,7% of primary open angle glaucoma patients of European origin. Molecular modeling predicted a decreased affinity of neurotrophin 4 protein (NT-4) mutants with its specific tyrosine kinase receptor B (TrkB). Expression of recombinant NT-4 carrying the most frequent mutation was demonstrated to lead to a decreased activation of TrkB. These findings suggest a novel pathway in the pathophysiology of glaucoma trough loss of neurotrophic function and may eventually open the possibility to use ligands activating TrkB to prevent the progression of the disease.
F. Pasutto. Institute of Human Genetics, Erlangen, Germany.
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.6 Cellular biology (Part of: 3 Laboratory methods)
