| Popis: |
Brain derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-related kinase receptor B (TrkB) play a protective role in the survival of retinal ganglion cells (RGCs) in healthy and disease states. SH2 domain tyrosine phosphatase PTPN11 (Shp2) is a ubiquitously expressed tyrosine phosphatase that regulates TrkB receptor and its activation is mediated through its interactions with the adapter protein Caveolin (Cav-1). This study determines the involvement of Cav-1 in facilitating Shp2 mediated inner retinal effects by genetically upregulating Shp2 expression in Cav-1 knockout mice.Shp2 was over-expressed in mice retina (n=38) through intravitreal injection of recombinant adeno-associated virus vector (AAV2). Wildtype and Cav-1 transgenic mice were used and for each animal one eye was transduced with PTPN11 transgene whereas GFP expression in the contralateral eye was used as control. Retinal functional changes were assessed by electroretinogram (ERG) and scotopic threshold response (STR) recordings. In vivo imaging using optical coherence tomography (OCT) and histological analysis were used to evaluate structural changes in the retinal laminar structure. Shp2 upregulation resulted in significantly reduced STR amplitude in both WT and Cav-1+/- mice (p |
