A novel pathway regulating adipogenesis in Thyroid Eye Disease: characterization of spontaneous lipogenesis and validation of novel therapeutic targets

Principal Investigator Dr Maryse Bailly
Dr Bailly is a Reader in Cell Biology at UCL and leads the “Tissue contraction, scarring and mechanoregulation” research lab at the UCL Institute of Ophthalmology

PhD student Dr I-Hui Yang
Dr I-Hui Yang is an ophthalmologist and oculoplastic surgeon from Taiwan, who came to do a PhD in Dr Bailly’s lab in May 2015, with a prestigious bursary from the Kaohsung Chang Gung Memorial Hospital (Taiwan).

Thyroid Eye Disease (TED) is a severe and potentially blinding disease of the tissues behind the eyeball, commonly affecting patients with thyroid problems. Fat and muscles in the orbit, the bony socket where the eye sits, swell and scar, perturbing eye movements and pushing the eye forward. This gives patient a staring ‘eye-bulging’ appearance, which creates significant social stigma, and leads to double vision, dry eyes, corneal damage, and potential sight-threatening compression of the optic nerve. TED is poorly understood and treatment options are limited, often leaving patients with permanent disfigurement and double vision. Most of the swelling in TED results from an expansion of the fat behind the eyeball, as local cells, called fibroblasts, turn into fat cells. However, why and how those cells change in TED is still unclear, preventing significant developments in prevention and treatment.

To better understand how fibroblasts turn into fat in TED, our team has grown patient cells in soft gels made of collagen, an essential component of the tissues in the orbit. Under such conditions, fibroblasts from patients spontaneously produce fat, mirroring what happens in TED. Our preliminary study of the cell characteristics and the type of fat they make suggests that fibroblasts in TED do not produce fat as classically found in the main body (such as belly fat), but rather make fat from sugars (a process termed de novo lipogenesis) and/or absorb more fat from the circulation. This project aims to confirm these findings and identify how the cells do this on a molecular level.

TED affects an estimated 400,000 people in the UK. In over 90% of cases, expansion of orbital tissues and fat are responsible for most of the detrimental disease manifestations, and thus an understanding of how this happens is crucial to the development of suitable treatments. Through exploring novel mechanisms driving fat accumulation in orbital cells, this project will identify potential new therapeutic targets that may provide better disease management options for the patients.

See the Fight for Sight website for more information about this research.