Chui Jeanie, Di Girolamo Nick, Coroneo Minas T, Wakefield Denis
Inflammatory Diseases Research Unit, Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4482-9. doi: 10.1167/iovs.07-0123.
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 (NK(1) receptor) in directing cell migration in pterygia that may explain the characteristic growth pattern.
Immunohistochemical analysis for SP and the NK(1) 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.
SP and NK(1) receptors were localized to infiltrating fibroblasts, mononuclear cells and the epithelia of pterygium, conjunctiva, and limbus, with elevated NK(1) 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 NK(1) receptor antagonist. Pterygium epithelial cells were not migratory in these experiments.
For the first time, this study showed the presence of NK(1) 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.
翼状胬肉是一种常见的眼表疾病，被认为是由角膜缘长期紫外线损伤引发的。翼状胬肉的一个神秘特征是其翼状形态，而支持其向心性生长的机制仍有待阐明。由于翼状胬肉的生长模式反映了角膜神经的放射状排列，作者提出神经肽可能促进其定向生长。这一假设促使对感觉神经肽P物质（SP）及其受体（NK(1)受体）在翼状胬肉细胞迁移导向中的作用进行研究，这可能解释其特征性的生长模式。
对5例翼状胬肉标本及其相应的自体结膜和角膜缘进行SP和NK(1)受体的免疫组织化学分析。采用改良的博伊登小室评估翼状胬肉上皮细胞、成纤维细胞和血管内皮细胞向SP的迁移情况。
SP和NK(1)受体定位于浸润的成纤维细胞、单核细胞以及翼状胬肉、结膜和角膜缘的上皮细胞，在翼状胬肉中观察到NK(1)受体染色增强。纳摩尔浓度的SP以剂量依赖方式诱导翼状胬肉成纤维细胞和血管内皮细胞迁移，这种迁移被NK(1)受体拮抗剂抑制。在这些实验中，翼状胬肉上皮细胞不具有迁移性。
本研究首次表明翼状胬肉中存在NK(1)受体，且SP是翼状胬肉成纤维细胞和血管内皮细胞的有效趋化剂，这意味着SP可能通过其促纤维化和促血管生成作用对翼状胬肉的形态产生影响。
