DENDRITIC CELLS & IMMUNE RESPONSE IN CORNEAL TISSUE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 板层角膜屈光手术（通常用于矫正近视、远视和散光的手术，如LASIK、LASEK、LAS IK和CK）导致上皮手术损伤附近基质中的角膜细胞凋亡。这种细胞凋亡又导致邻近角膜细胞的活化、成纤维细胞和肌成纤维细胞的转化和迁移以及细胞外基质的改变。这些事件包括细胞因子释放的上调和炎性细胞对伤口部位的趋化性。尽管大多数患者愈合而没有并发症，但一些患者发展为称为“干眼”的状态，其特征在于干燥的眼表面和营养因子的丧失，这导致上皮破裂和炎症增加，这在某些情况下可导致异常瘢痕形成和视力损害。导致角膜正常或异常愈合的不同信号知之甚少。我们的假设是，“巨噬细胞或树突状细胞功能的差异可能部分决定角膜是否有足够的愈合或屈光手术后愈合过程受损”。因此，我们将把我们的研究重点放在表征的巨噬细胞和树突状细胞（DC），抗原呈递细胞和炎症介质诱导屈光手术，在正常或异常愈合的模型。所提出的研究使用小鼠角膜中的角膜上皮细胞作为实验模型。这项研究的长期目标是了解导致手术后角膜异常愈合的机制，并开展临床研究以测试免疫反应的调节是否可以预防或逆转异常愈合。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lamellar corneal refractive surgery (procedures such as PRK, LASEK, LAS IK and CK that are commonly performed to correct myopia, hyperopia and astigmatism) leads to keratocyte apoptosis in the stroma adjacent to the epithelial surgical injury. This apoptosis, in turn, leads to activation of adjacent keratocytes, transformation and migration of fibroblasts and myofibroblasts, and alterations of the extracellular matrix. These events include an up-regulation of cytokine release and chemotaxis of inflammatory cells to the wound site. Although most patients heal without complications, some develop a state called "dry eye" characterized by a dry ocular surface and loss of trophic factors that leads to epithelial breakdown and increased inflammation which can, in some cases lead to abnormal scarring and vision impairment. The different signals that lead to normal or abnormal healing of the cornea are poorly understood. Our hypothesis is that "differences in macrophage or dendritic cell function may in part determine whether there is an adequate healing of the cornea or there is an impaired healing process after refractive surgery". We will therefore focus our studies on the characterization of macrophages and dendritic cells (DC), both antigen presenting cells and the inflammatory mediators induced by refractive surgery, in models of normal or abnormal healing. The proposed studies use PRK in mouse cornea as the experimental model. The long-term goal of this research is to understand the mechanisms leading to abnormal healing of the cornea after surgery, and develop clinical studies to test whether modulation of the immune response can prevent or reverse abnormal healing.