EFFECT OF VITAMIN A DEFICIENCY ON LEUKOCYTE FUNCTION

维生素A缺乏是全世界儿童失明的主要原因。 随着缺损量的增加，角膜变得角质化， 易患角膜溃疡(角膜软化)。维生素A缺乏 儿童由于对感染的易感性增加，患病率更高。 发病率和死亡率比正常同龄人更高 地理区域。了解炎症过程异常的原因 对维生素A缺乏儿童的治疗很重要。 该项目的长期目标是阐明维生素A的作用 在角膜炎症过程中的缺陷。这笔赠款是 针对中性粒细胞，一个主要的介导者 角膜发炎。 具体目标如下： 1)测定维生素A缺乏对人体健康影响的时程 角膜和体外检测多形核白细胞功能。 2)体外测定添加视黄醇、维甲酸和 视网膜恢复体外检测中性粒细胞功能。 3)确定体内给药治疗剂量的效果 维生素A对角膜和体外多形核白细胞的影响 用药后第1、2、8、16天。 4)确定与中性粒细胞有关的反应 功能被改变。 维生素A缺乏症大鼠模型分为早、中、晚三个阶段 缺乏症。体内功能将使用角膜模型进行测试 铜绿假单胞菌所致角膜炎 它能够诱导受控的中性粒细胞反应。 外周中性粒细胞的数量和数量将在体外进行表征 成熟度，静息状态和活动状态的稳定性，抗化学药物的能力 在刺激下，吞噬、杀灭和消化细菌 和非刺激条件。中性粒细胞参与的反应和/或机制 将涉及激活、杀戮、消化和自我保护。 光镜和电子显微镜、荧光细胞流、酶和细胞 将使用生物学技术。

Vitamin A deficiency is the leading cause of childhood blindness worldwide. With increasing deficiency the cornea becomes keratinized and is susceptible to corneal ulceration (keratomalacia). Vitamin A deficient children, because of an increased susceptibility to infections, have higher morbidity and mortality rates than their normal peers from the same geographical area. Understanding why the inflammatory process is abnormal is important in the treatment of a vitamin A deficient child. The long term goal of this project is to elucidate the effects of vitamin A deficiency on the inflammatory process in the cornea. This grant is directed towards the polymorphonuclear leukocyte, a major mediator of corneal inflammation. The specific aims are the following: 1) To determine the time course of the effects of vitamin A deficiency on corneal and in vitro tested polymorphonuclear leukocyte functions. 2) To determine the ability of in vitro added retinol, retinoic acid and retinal to restore in vitro tested polymorphonuclear leukocyte function. 3) To determine the effect of in vivo administered therapeutic doses of vitamin A on corneal and in vitro tested polymorphonuclear leukocyte function 1, 2, 8 and 16 days after administration. 4) To determine which reactions involved in polymorphonuclear leukocyte function are altered. The rat model of vitamin A deficiency will be used at early, mid and late deficiency. In vivo function will be tested using the corneal model of Pseudomonas keratitis with a strain of Pseudomonas aeruginosa chosen for its ability to induce a controlled polymorphonuclear leukocyte response. Peripheral PMNs will be characterized in vitro as to their number and maturity, stability in the resting and active states, ability to chemotax towards a stimulus, phagocytose, kill and digest bacteria under stimulated and non-stimulated conditions. Reactions and/or mechanism involved in PMN activation, killing, digestion and self-protection will be addressed. Light and electron microscopy, fluorescence cytoflow, enzymatic and cell biology techniques will be used.