Dual TSHR/IGF-1Rα electroporation induces progressive orbital remodeling and retinochoroidal alterations in a murine model of thyroid eye disease.

BACKGROUND

Thyroid eye disease (TED) is an autoimmune disorder strongly associated with thyroid dysfunction. Its pathogenesis encompasses both hyperthyroidism and progressive pathological alterations in orbital tissues.

METHODS

A TED animal model was induced via dual-plasmid electroporation. Serum levels of thyroid hormones (T4), thyroid-stimulating hormone (TSH), TSH receptor antibodies (TRAb), and thyroid-stimulating blocking antibodies (TSBAb) were quantified by ELISA to evaluate thyroid function. Intraocular pressure (IOP) was monitored using a tonometer. Optical coherence tomography (OCT) was employed to measure thickness changes in the retinal nerve fiber layer (RNFL), choroid (Ch), and retinal neuroepithelial layer (RNEL). Magnetic resonance imaging (MRI) was utilized to assess exophthalmos and orbital volume, enabling a comprehensive evaluation of structural and pathological alterations in TED.

RESULTS

Thyroid dysfunction was initially observed after the fourth immunization. By the seventh immunization, MRI confirmed fibrotic remodeling of orbital tissues, accompanied by significant enlargement of orbital volume and increased exophthalmos. OCT analysis revealed a statistically significant increase in mean retinal nerve fiber layer thickness (RNFLT) following the ninth immunization. Mean choroidal thickness (ChT) exhibited a progressive thickening trend from the fourth immunization onward. Although a slight increase in mean retinal neuroepithelial layer thickness (RNELT) was noted, this change was not statistically significant.

CONCLUSION

The findings indicate that the progression of TED exhibits distinct temporal characteristics: the disease is primarily driven by autoantibodies, particularly TSHR antibodies, which subsequently lead to thyroid dysfunction. This thyroid dysfunction further precedes and facilitates pathological alterations in orbital structures, with orbital fibrosis being a critical component of disease progression. Furthermore, OCT serves as a valuable non-invasive imaging modality for monitoring microstructural changes in the retina and choroid in TED. This study provides foundational insights into TED pathogenesis and supports the development of integrated assessment strategies.