Exploring Disease Characteristics During the Latent Phase of Graves’ Orbitopathy: Insight from a Mouse Model

Objective: The objective is to utilize a multimodal analysis model to examine the developmental process from Graves’ disease (GD) to Graves’ Orbitopathy (GO) in mice, investigate T-cell changes during the GO latent phase, and lay the groundwork for exploring the therapeutic window for GO. Method: The GO model was induced in BALB/c female mice using plasmids containing thyrotropin receptor (TSHR) A subunit (pcDNA3.1/TSHR289) and insulin-like growth factor 1 receptor (IGF-1R) α subunit (pcDNA3.1/IGF-1Rα), respectively, in combination with electroporation immunization. Signs in the mice, as well as serological, imaging and histological information, were collected at predetermined time points for analysis. Results: After the 4th immunization, the mice gradually developed symptoms such as tearing and photophobia. After the 7th immunization, obvious protrusion of the eyeballs could be observed. This study successfully established a GO mouse model after the 7th immunization, with a success rate of 84.6% (11/13). During the progression from GD to GO, the upward trend of TSAb is slightly slower than that during the GD period. And the proportions of Th1 and Th17 cells significantly increased and stabilized after disease stabilization, while Th2 and Treg cells showed a decreasing trend. The increase in collagen fibers and hyaluronic acid persisted throughout the process and remained at a high level after disease stabilization. Conclusion: This study successfully established a GO mouse model after the 7th immunization and performed multimodal analysis, proposing the concept of “GO latency period” in an animal model for the first time. In particular, changes in the GO latency period were analyzed in depth, establishing the foundation for determining the therapeutic window for GO and preventing its onset and progression.