Development of a Novel Thyroid Function Fluctuated Animal Model for Thyroid-Associated Ophthalmopathy

作者：Tu, Yunhai; Wang, Yilong; Ding, Luna; Zhang, Jiao; Wu, Wencan^*

来源：PLos One, 2016, 11(2): e0148595.

DOI：10.1371/journal.pone.0148595

• GRAVES-OPHTHALMOPATHY
• THYROTROPIN RECEPTOR
• CURRENT INSIGHTS
• DISEASE
• ORBITOPATHY
• HYPERTHYROIDISM
• EXPRESSION
• AUTOANTIBODIES
• PATHOGENESIS
• ANTIBODIES

Background @@@ The establishment of a suitable and stable animal model is critical for research on thyroid-associated ophthalmopathy (TAO). In clinical practice, we found that patients treated with I-131 often exhibit TAO; therefore, we aimed to establish a novel thyroid function fluctuated animal model of TAO by simulating the clinical treatment process. @@@ Methods @@@ We treated SD rats with I-131 to damage the thyroid and then used sodium levothyroxine (L-T4) to supplement the thyroid hormone (TH) levels every seven days, leading to a fluctuating level of thyroid hormones that simulated the status of clinical TAO patients. Rats administered normal saline were considered as a control. The weight, intraocular pressure, and serum T3, T4, TSH and TRAb levels of the rats were measured, and the pathological changes were analyzed by H& E staining and transmission electron microscopy (TEM). @@@ Results @@@ The experimental rats (TAO group) exhibited significantly reduced weight and elevated intraocular pressure compared with the control rats. Meanwhile, the serum levels of T3 and T4 were up-regulated in the TAO group, but the TSH level decreased during the 10-week study. Moreover, increased numbers of blood vessels and inflammatory cell infiltrations were observed in the orbital tissues of the TAOrats, while no abnormal changes occurred in the control rats. The orbital myofibrils in the TAO rats appeared fractured and dissolved, with twisted structures. Mitochondrial swelling and vacuoles within the endoplasmic reticulum, swelling nerve fibers, shedding nerve myelin, and macrophages were found in the TAO group. @@@ Conclusion @@@ Rats treated with I-131 and sodium levothyroxine exhibited characteristics similar to those of TAO patients in the clinic, providing an effective and simple method for the establishment of a stable animal model for research on the pathogenesis and treatment of TAO.

• 出版日期2016-2-12
• 单位温州医科大学