Teprotumumab reduces the proliferation and viability of pterygium fibroblasts

Abstract

Pterygium is a fibrovascular overgrowth on the ocular surface. There is no effective medical treatment, and the high rate of postoperative recurrence remains a major clinical challenge. We aimed to investigate the ability of teprotumumab (TPT), an insulin-like growth factor 1 receptor antagonist, to reduce human pterygium fibroblast (HPF) viability and proliferation. Primary HPF cultures were derived from excised pterygium tissues from 10 patients scheduled for pterygium surgery, and treated with 10 mg/mL TPT. Cell viability and proliferation were evaluated. DNA damage was measured with TUNEL staining, and ultrastructural changes were visualized by electron microscopy. Quantitative polymerase chain reaction was used to assess the expression of genes involved in growth factor signaling, angiogenesis, and extracellular matrix remodeling. Primary HPF cell lines were successfully established from 5/10 patients. Treatment with TPT significantly reduced HPF viability (29.5 %–50 %) and proliferation (32 %–67 %) across all tested lines. Ki-67-positive cell counts decreased markedly, corroborating the reduced proliferative capacity. TUNEL staining and electron microscopy revealed extensive DNA damage, nuclear fragmentation, and vacuolization. TPT modulated gene expression by downregulating FGF2, VEGFA, and PAI-1 expression while upregulating MMP2 and MMP3 expression, suggesting reduced fibroblast activity and angiogenesis with enhanced extracellular matrix remodeling. TPT demonstrated robust antifibrotic effects on HPFs by reducing their viability and proliferation, inducing DNA damage, and altering the expression of genes associated with fibrosis and angiogenesis. These findings position TPT as a promising therapeutic agent for pterygium, potentially addressing postoperative recurrence and progression. Future animal studies and clinical trials are needed to confirm its efficacy and safety in clinical settings.