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Regulation of TrkB activity by PTPN11 is mediated through transmembrane protein Caveolin in the inner retina

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thesis
posted on 29.03.2022, 03:14 by Mojdeh Abbasi
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<0.001 and p<0.01 respectively). Cav-1-/- group on the other hand demonstrated only a slight loss of STR amplitudes upon Shp2 upregulation that was statistically insignificant. Cellular density in the ganglion cell layer (GCL) was also significantly reduced in WT and Het groups (p<0.001 and p<0.01 respectively). Shp2 upregulation did not result in a significant decrease in the GCL density in Cav-1-/- mice. Together, these results suggest a novel role of Cav-1 in mediating Shp2 actions in retina particularly RGCs. Loss of Cav-1 exerts a protective effect particularly on the inner retinal function and structure. Future studies will help establish the pathophysiological cross talk between these two proteins.

History

Table of Contents

Chapter 1. Introduction -- Chapter 2. Methods -- Chapter 3. Results -- Chapter 4. Discussion -- Conclusion -- References.

Notes

Empirical thesis. Bibliography: pages 69-89

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

MRes, Macquarie University, Faculty of Medicine and Health Sciences, Department of Clinical Medicine

Department, Centre or School

Department of Clinical Medicine

Year of Award

2016

Principal Supervisor

Stuart Graham

Additional Supervisor 1

Vivek K. Gupta

Additional Supervisor 2

Seyyed Mojtaba Golzan

Rights

Copyright Mojdeh Abbasi 2016. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (ix, 89 pages) colour illustrations

Former Identifiers

mq:69682 http://hdl.handle.net/1959.14/1256695