Coexpression of IGF1R and TSHR in extraocular muscles of patients with thyroid-associated orbitopathy

To explore the roles of insulin-like growth factor 1 receptor (IGF1R) and thyroid-stimulating hormone receptor (TSHR) in extraocular muscle pathology.

Extraocular muscle specimens were obtained during rectus muscle myectomy surgeries performed for large-angle strabismus correction in patients with thyroid-associated orbitopathy (TAO) and during rectus muscle resection surgeries performed for congenital strabismus in normal controls. Immunohistochemistry was employed to detect and compare between-group IGF1R and TSHR expression; ImageJ software was used to assess the staining area and H&E staining was used to evaluate morphological differences in tissues. Intergroup comparisons were conducted using the Mann-Whitney U test.

Histological examination of the extraocular muscle specimens revealed greater fibrosis in the TAO group (n=12) than in the control group (n=6). Immunohistochemistry (IHC) revealed significantly higher expression of both IGF1R and TSHR in the TAO group, particularly in elongated fibroblast-like cells and some myocytes, than in the control group, which exhibited minimal expression. Semiquantitative analysis confirmed significantly larger mean expression areas for IGF1R and TSHR in the TAO group than in the control group (p<0.05).

Our study revealed elevated IGF1R and TSHR expression in the extraocular muscles of patients with TAO, supporting their potential involvement in orbital fibroblast infiltration and muscle remodelling in TAO. These findings provide tissue-based support for the biological relevance of IGF1R in TAO-related extraocular muscle pathology and may help inform future investigations of IGF1R-targeted therapies such as teprotumumab. Further quantitative and mechanistic studies are warranted to better define the therapeutic implications of these findings.