title: Development of a Novel Thyroid Function Fluctuated Animal Model for Thyroid-Associated Ophthalmopathy.
abstract: 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 TAO rats, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Laboratory Animal Center, Wenzhou Medical University, Wenzhou, 325000, PR China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
authors.forename: Luna
authors.initials: L
authors.lastname: Ding
authors.affiliation: The Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
authors.forename: Wencan
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D049970:Graves Ophthalmopathy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007429:Intraocular Pressure; D007457:Iodine Radioisotopes / Q000009:adverse effects; D008933:Mitochondrial Swelling; D009210:Myofibrils / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009915:Orbit / Q000098:blood supply / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism; D013974:Thyroxine / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014284:Triiodothyronine / Q000235:genetics / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine