Pasutto, Francesca and Matsumoto, Tomoya and Mardin, Christian Y. and Sticht, Heinrich and Brandstaetter, Johann H. and Michels-Rautenstrauss, Karin and Weisschuh, Nicole and Gramer, Eugen and Ramdas, Wishal D. and van Koolwijk, Leonieke M. E. and Klaver, Caroline C. W. and Vingerling, Johannes R. and Weber, Bernhard H. F. and Kruse, Friedrich E. and Rautenstrauss, Bernd and Barde, Yves-Alain and Reis, Andre (2009) Heterozygous NTF4 Mutations Impairing Neurotrophin-4 Signaling in Patients with Primary Open-Angle Glaucoma. AMERICAN JOURNAL OF HUMAN GENETICS, 85 (4). pp. 447-456. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
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. Although members of the neurotrophin 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 the 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 (NIT-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 decreased activation of TrkB. These findings suggest a pathway in the pathophysiology of glaucoma through loss of neurotrophic function and may eventually open the possibility of using ligands activating TrkB to prevent the progression of the disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RETINAL GANGLION-CELLS; IN-VIVO; CYP1B1 MUTATIONS; GERMAN PATIENTS; NEURONAL DEATH; GENE; EXPRESSION; SURVIVAL; TRKB; POPULATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Sep 2020 09:07 |
| Last Modified: | 03 Sep 2020 09:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28280 |
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