Development and application of animal models to study thyroid-associated ophthalmopathy

Thyroid-associated ophthalmopathy (TAO), also known as Graves' ophthalmopathy, is an autoimmune disease that is usually accompanied by hyperthyroidism. Its pathogenesis involves the activation of autoimmune T lymphocytes by a cross-antigen reaction of thyroid and orbital tissues. The thyroid-stimulating hormone receptor (TSHR) is known to play an important role in the development of TAO. Because of the difficulty of orbital tissue biopsy, the establishment of an ideal animal model is important for developing novel clinical therapies of TAO. To date, TAO animal modeling methods are mainly based on inducing experimental animals to produce anti-thyroid-stimulating hormone receptor antibodies (TRAbs) and then recruit autoimmune T lymphocytes. Currently, the most common methods are hTSHR-A subunit plasmid electroporation and hTSHR-A subunit adenovirus transfection. These animal models provide a powerful tool for exploring the internal relationship between local and systemic immune microenvironment disorders of the TAO orbit, facilitating the development of new drugs. However, existing TAO modeling methods still have some defects, such as low modeling rate, long modeling cycles, low repetition rate, and considerable differences from human histology. Hence, the modeling methods require further innovation, improvement, and in-depth exploration.