The role of Src family kinases in Thyroid Eye Disease.

• Research type

  Research Study

• Full title

  The role of Src family kinases in Thyroid Eye Disease: disease mechanisms and therapeutic potential

• IRAS ID

  158488

• Contact name

  Daniel Ezra

• Contact email

  d.ezra@ucl.ac.uk

• Sponsor organisation

  Moorfields Eye Hospital NHS Foundation Trust

• Duration of Study in the UK

  3 years, 0 months, 1 days

• Research summary

  Thyroid eye disease (TED) is a common disorder affecting patients with thyroid disease, most commonly, Graves disease. The main feature of TED is the Protrusion of the eyes as a result of an increase in the volume of the tissues of the eye socket behind the eye. These changes can be dramatic and can cause disfigurement and blindness.

  Clinical manifestations include extraocular muscle fibrosis and upper lid retraction, as well orbital fat inflammation and expansion, causing eye bulging. These pathological processes are thought to be mediated by transdifferentiation of resident fibroblast cells into fat and scarring cells within the orbit. However, the disease mechanisms and the stimuli that regulate cell transdifferentiation are unknown, preventing any significant development in prevention and treatment. Our preliminary work on orbital fibroblasts(cells) isolated from TED patients has shown that TED fibroblasts display a characteristic dual pro-scarring (profibrotic) and fat - generating (adipogenic) phenotype in vitro. Both the profibrotic matrix contraction profile and adipogenesis could be modulated by special molecules called Src kinase family (SFK) inhibitors, suggesting that SFK activity may underlie TED pathogenesis. The aim of this project is thus to test the hypothesis that the specific dual phenotype of TED cells is due to an increase in SFKs activity, and to characterise the pathways involved to identify new treatment options.

  We need to collect the following tissues (which would normally be discarded):

  • Eye socket fat tissue from 10 patients with TED
  • Eye socket fat tissue from 10 patients without TED

  This study is being sponsored by Moorfields Eye Hospital, and is being funded by a grant from Fight For Sight.

• REC name

  East Midlands - Leicester Central Research Ethics Committee

• REC reference

  14/EM/1186

• Date of REC Opinion

  7 Oct 2014

• REC opinion

  Favourable Opinion