NEURAL CONTROL OF LACRIMAL GLAND SECRETION

泪腺分泌的神经控制

基本信息

批准号：
2684550
负责人：
BENJAMIN WALCOTT
金额：
$ 22.69万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-01-01 至 1999-11-30
项目状态：
已结题

项目摘要

Dry eye is a painful, debilitating and often serious condition that is observed particularly in older women. It is characterized by an inability of the tear glands to produce sufficient tear fluid to wet the ocular surface and often results in inflammation and damage to the cornea and conjunctiva. At best, the condition is painful and requires the regular use of eye drops and at worst, if untreated, it can result in significant loss of visual acuity due to damage to the cornea. There are a number of different disease conditions that can cause the lacrimal glands to reduce or stop their secretion but one of the most common and well characterized is Sjorgen's syndrome. In this disease, the lacrimal glands (and salivary glands as well) become infiltrated with large numbers of lymphocytes from the immune system that destroy portions of the lacrimal gland tissue yet the remaining apparently normal appearing tissue is unable to function. The basic question, then, is why doesn't the rest of the gland continue to function. The MRL and NZB strains of mice are useful models of the disease condition and will be used along with normal mice in anatomical and physiological studies to determine what processes in the stimulus-secretion pathway have been affected by the disease.Immunocytochemistry will be used to detail the normal pattern of innervation of the lacrimal glands and to determine the neurotransmitters present. Examination of diseased glands from the MRL and NZB mice will determine what effects the infiltration has on the innervation. Experiments using isolated glands from normal and diseased animals will show whether secretion can be induced by the exposure of the tissue to known excitatory neurotransmitters and other stimulatory agents. Finally, cells will be isolated from normal and diseased glands and patch-clamp techniques will be used to characterize the ion channels present on the surface membranes of the secretory cells and to determine the changes that occur in the disease states. Such ion channels are important in the fluid transport process of the gland and are a reliable measure of its activity. These studies, therefore, will determine at what point(s) ina the stimulus-secretion process the disease process of Sjogren's syndrome is breaking the link and will assist in the process of finding a treatment to ameliorate the symptoms at least while normal tissue is still present.

干眼症是一种痛苦、使人衰弱且通常很严重的疾病，尤其是在老年妇女中观察到。它的特点是无能力泪腺产生足够的泪液来湿润眼睛表面并经常导致炎症和角膜损伤结膜。充其量，这种情况是痛苦的，需要定期治疗使用眼药水，在最坏的情况下，如果不治疗，可能会导致严重的后果由于角膜损伤而导致视力丧失。有许多可能导致泪腺减少的不同疾病状况或停止分泌，但这是最常见和最明确的特征之一是Sjorgen 综合征。在这种疾病中，泪腺（和唾液腺体）被大量淋巴细胞浸润免疫系统尚未破坏部分泪腺组织其余看似正常的组织无法发挥作用。那么，基本问题是为什么腺体的其余部分不继续功能。 MRL 和 NZB 品系小鼠是该疾病的有用模型条件并将与正常小鼠一起用于解剖学和生理学研究以确定刺激分泌过程途径已受到疾病的影响。将使用免疫细胞化学详细说明泪腺神经支配的正常模式并确定存在的神经递质。检查患病腺体来自 MRL 和 NZB 小鼠的结果将确定渗透的影响关于神经支配。使用正常和分离的腺体进行的实验患病动物会显示暴露是否可以诱导分泌组织对已知的兴奋性神经递质和其他刺激物的影响代理。最后，细胞将从正常和患病的腺体中分离出来膜片钳技术将用于表征离子通道存在于分泌细胞的表面膜上并确定疾病状态发生的变化。这样的离子通道是在腺体的液体运输过程中很重要，是可靠的衡量其活性。因此，这些研究将决定在什么情况下刺激-分泌过程中的点疾病过程干燥综合症正在打破这种联系，并将有助于这一过程找到至少在正常组织的情况下改善症状的治疗方法仍然存在。