IMMUNE RESPONSES IN MACULAR DEGENERATION

描述(申请人描述)：老年性黄斑变性(ARMD) 是一种进行性视网膜疾病，发生在50岁以上的人群中 与视力丧失有关，再加上一系列特定的临床症状， 生理和组织病理学特征。黄褐斑的致病机制 这些具体的变化是未知的，但间接证据表明 ARMD中巨噬细胞介导的成分。我们提出了一般假设 ARMD患者脉络膜巨噬细胞为血源性单核细胞 被招募到脉络膜毛细血管，以清除被困在 布鲁赫膜。在这个项目中，我们提出了两个具体的目标来探索 巨噬细胞在与ARMD相关的条件下被激活。在目标1中，我们将使用 新鲜分离的正常人或ARMD患者的单核细胞，以 确定高活性和低活性单核细胞的存在，并确定 高活动度是ARMD进展的一个预后标志。在Aim 2中，使用 最近建立的与年龄相关的RPE细胞外沉积的小鼠模型 我们实验室开发的，我们将在小鼠体内诱导高活性单核细胞，并 确定这些巨噬细胞将增加RPE变性的严重程度 或矿床形成的进度。

DESCRIPTION (Applicant's Description): Age-related macular degeneration (ARMD) is a progressive disorder of the retina occurring in people older than age 50 associated with vision loss coupled with a spectrum of specific clinical, physiological and histopathological features. The pathogenic mechanisms for these specific changes are unknown, but circumstantial evidence suggests a role for a macrophage-mediated component in ARMD. We propose the general hypothesis that choroidal macrophages observed in ARMD are blood-derived monocytes recruited to the choriocapillaris to scavenge debris and deposits trapped in Bruch's membrane. In this project, we propose two specific aims to explore macrophage activation under conditions relevant to ARMD. In aim 1, we will use freshly isolated blood monocytes from normal subjects or ARMD patients, to establish the existence of high and low activity monocytes and to determine if high activity is a prognostic marker for ARMD progression. In aim 2, using a mouse model for age-related subRPE extracellular deposit formation recently developed in our laboratory, we will induce high activity monocytes in mice and establish that these macrophages will increase the severity of RPE degeneration or rate of progression of deposit formation.