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C. J. Hwang, R. S. Douglas, T. J. Smith; Novel Mouse Model for Thyroid-Associated Ophthalmopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2399.
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Thyroid-associated ophthalmopathy (TAO) affects 10-45% of patients with Graves’ disease manifesting as inflammation, proptosis, and occasionally blindness. The pathogenesis of TAO is poorly understood, but is likely related to an underlying autoimmune process. Our laboratory is currently investigating the immunologic factors associated with TAO and has found that the insulin-like growth factor receptor (IGFR) may be integral in the disease process.Patients affected by Graves’ disease have a spectrum of orbital disease ranging from those that have predominantly extraocular muscle enlargement to those that have predominantly orbital fat expansion. Many investigators have tried to develop a mouse model for TAO, but to date there are no mouse models that can replicate the orbital disease found in these patients. We have developed a novel technique for studying the fat component of TAO in a severe combined immune deficiency (SCID) mouse model.
Orbital fat with informed consent was obtained from patients undergoing orbital decompression for TAO and from normal patients undergoing blepharoplasty with fat removal. Tissue was washed, volumetrically measured, and implanted under the flank skin of SCID mice. Mice (n=20) were monitored for 12 weeks and the implants were removed for mass and histological evaluations.
The xenografts were fully vascularized and viable upon harvesting. There were no significant differences in pre-implantation and post-implantation mass in both TAO and normal xenografts. Histological examination was performed on pre-implantation and post-implantation fat for H&E, COX2/Collagen VI, and IGFR. There were no significant differences between pre- and post-implantation fat histologically, however, there was a difference between the histology between TAO and normal fat. In TAO fat, there was more fibrosis, mononuclear infiltrate, and IGFR staining compared to normal.
We present a reliable animal model for in vivo examination of the fat component of thyroid-associated ophthalmopathy. On histological examination, there is no change pre-and post-implantation and the xenografts are fully viable and vascularized upon harvesting. This model will allow us to expand our understanding of the role of fibroblasts in Graves’ disease. Future studies will be in developing therapies targeted at the orbital fat component in thyroid-associated ophthalmopathy.
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