Induction of Apoptosis in Pterygium Cells by Antagonists of Growth Hormone–Releasing Hormone Receptors

Purpose: The aim of the study was to investigate the signaling of growth hormone-releasing hormone receptor (GHRH-R) in the pathogenesis of pterygium and determine the apoptotic effect of GHRH-R antagonist on pterygium epithelial cells (PECs). Methods: Fourteen samples of primary pterygium of grade T3 with size of corneal invasion ≥ 4 mm were obtained for investigation by histology, immunofluorescence, electron microscopy, explant culture, and flow cytometry. Results: We found that PECs were localized in the basal layer of the epithelium in advancing regions of the head of pterygium. These cells harbored clusters of rough endoplasmic reticulum, ribosomes, and mitochondria, which were consistent with their aggressive proliferation. Immunofluorescence studies and Western blots showed that GHRH-R and the downstream growth hormone receptor (GH-R) were intensively expressed in PECs. Their respective ligands, GHRH and GH, were also elevated in the pterygium tissues as compared to conjunctival cells. Explanted PECs were strongly immunoreactive to GHRH-R and exhibited differentiation and proliferation that led to lump formation. Treatment with GHRH-R antagonist MIA-602 induced apoptosis of PECs in a dose-dependent manner, which was accompanied by a downregulation of ERK1 and upregulation of Caspase 3 expression. Conclusions: Our results revealed that GHRH-R signaling is involved in survival and proliferation of PECs and suggest a potential therapeutic approach for GHRH-R antagonist in the treatment of pterygium.