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The Role of Substance P in the Pathogenesis of Pterygia

¹From the Inflammatory Diseases Research Unit, Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia; and the ²Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia.

PURPOSE. Pterygium is a prevalent ocular surface disorder thought to be triggered by chronic ultraviolet damage to the limbus. One of the enigmatic features of pterygium is its wing-like shape, and the mechanism(s) supporting its centripetal growth remain to be elucidated. Because the growth pattern of pterygia mirrors the radial arrangement of corneal nerves, the authors propose that neuropeptides may facilitate its directional growth. This hypothesis prompted an investigation of the role of the sensory neuropeptide substance P (SP) and its receptor (NK₁ receptor) in directing cell migration in pterygia that may explain the characteristic growth pattern.

METHODS. Immunohistochemical analysis for SP and the NK₁ receptor was performed on five pterygium specimens with corresponding autologous conjunctiva and limbus. Migration of pterygium epithelium, fibroblasts, and vascular endothelial cells toward SP was assessed by using a modified Boyden chamber.

RESULTS. SP and NK₁ receptors were localized to infiltrating fibroblasts, mononuclear cells and the epithelia of pterygium, conjunctiva, and limbus, with elevated NK₁ receptor staining observed in pterygia. SP at nanomolar concentrations induced cell migration in pterygium fibroblasts and vascular endothelium in a dose-dependent fashion, which was inhibited by an NK₁ receptor antagonist. Pterygium epithelial cells were not migratory in these experiments.

CONCLUSIONS. For the first time, this study showed the presence of NK₁ receptor in pterygia and that SP is a potent chemoattractant for pterygium fibroblasts and vascular endothelial cells, implying that SP may contribute to the shape of pterygia through its profibrogenic and angiogenic action.