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.
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