LSUHSC COBRE: PROJ 4: DENDRITIC CELLS & IMMUNE RESPONSE IN CORNEAL TISSUE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。板层角膜屈光手术（通常用于矫正近视、远视和散光的PRK、LASEK、lasik和CK等手术）会导致上皮手术损伤附近基质中的角化细胞凋亡。这种细胞凋亡反过来又导致相邻角化细胞的活化，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症细胞对伤口部位的趋化。虽然大多数患者愈合无并发症，但有些人会出现一种称为“干眼”的状态，其特征是眼表面干燥，营养因子丧失，导致上皮破坏和炎症增加，在某些情况下会导致异常疤痕和视力障碍。导致角膜正常或不正常愈合的不同信号尚不清楚。我们的假设是，“巨噬细胞或树突状细胞功能的差异可能在一定程度上决定了屈光手术后角膜的愈合是否充分，或者愈合过程是否受损”。因此，我们将重点研究在正常或异常愈合模型中巨噬细胞和树突状细胞（DC），抗原递呈细胞和屈光手术诱导的炎症介质的特性。本研究以小鼠角膜PRK为实验模型。这项研究的长期目标将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 will be to understand the mechanisms that lead 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.