AMELIORATION OF RECURRENT HERPES KERATITIS

描述：单纯疱疹病毒性角膜炎是感染性角膜炎的主要原因。 在美国失明。 视力丧失最常见的原因是 复发性基质病，而不是原发性疱疹性角膜炎。 最 实验模型集中于原发性而不是复发性角膜炎。 PI创建了复发性疱疹性角膜炎的动物模型， 人类 局灶性间质混浊、局部新生血管和 在复发性角膜炎模型中产生的内皮炎， 对照组为角化、利姆布斯至利姆布斯混浊和渗出 单纯疱疹病毒性角膜炎是一种常见的角膜炎。 NIH小鼠。 虽然目前的数据表明，原发性和复发性疱疹 角膜炎可能有一些共同的免疫机制，这是PI的假设 临床病理学、病毒抗原 角膜内的分布，以及对疫苗治疗的反应表明， 这两种疾病的免疫反应是不一样的 的 PI提出了一些研究，旨在验证HSK复发的假设， 在NIH近交系小鼠中，由Th 1表型的CD 4 + T细胞介导。 在 为了检验这一假设，他将：（1）定义细胞， 通过选择性耗竭对复发性疾病的共刺激需求 实验;（2）表征和比较角膜中的细胞因子谱 用ELISA和RT-PCR检测原发性和复发性角膜炎的组织 分析，然后确定这些细胞因子的相关性， 通过用单克隆抗体特异性靶向细胞因子来治疗疾病;（3） 确定是否用HSV-1的vhs突变株进行保护性疫苗接种 涉及选择性刺激Th 2介导的免疫应答。 的 从这些研究中获得的信息将有助于更好地了解 小鼠复发性单纯疱疹性角膜炎的生物学， 这种疾病在人类。 此外，这些研究可能表明， 旨在改善疱疹的更特异和有效的免疫疗法 单纯性角膜炎

DESCRIPTION: Herpes simplex keratitis is the leading cause of infectious blindness in the United States. Visual loss most commonly results from recurrent stromal disease, as opposed to primary herpes keratitis. Most experimental models have focused on primary rather than recurrent keratitis. The PI has created an animal model of recurrent herpetic keratitis in humans. The focal stromal opacification, regional neovascularization and endotheliitis produced in the recurrent keratitis model, is in distinct contrast to the keratinization, limbus to limbus opacification and exudative blepharoconjunctivitis that is seen in primary herpes simplex keratitis in NIH mice. While current data indicates that primary and recurrent herpes keratitis may share some common immune mechanisms, it is the PI's hypothesis that the considerable differences in the clinical pathology, viral antigen distribution within the cornea, and responses to vaccine therapy suggests that the immune responses in these two diseases will not be identical. The PI has proposed studies designed to test the hypothesis that recurrent HSK in NIH inbred mice is mediated by CD4+ T cells of the Th1 phenotype. In order to test this hypothesis he will: (1) define the cellular and costimulatory requirements for recurrent disease by selective depletion experiments; (2) characterize and compare the cytokine profile in corneal tissue during primary versus recurrent keratitis, using ELISA and RT-PCR analysis and then determine the relevance of these cytokines to recurrent disease by specifically targeting cytokines with monoclonal antibodies; (3) determine whether protective vaccination with a vhs-mutant strain of HSV-1 involves the selective stimulation of a Th2-mediated immune response. The information derived from these studies will lead to a better understanding of the biology of recurrent herpes simplex keratitis in mice and thereby this disease in humans. Furthermore, these studies could possibly suggest more specific and effective immunotherapies designed to ameliorate herpes simplex keratitis disease.