Water and Ion Transport in Lacrimal Gland: Models and Experiment
Huang, Wei Chieh
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Tear secretion is a complicated process that involves two different cell types. The lacrimal acinar cell is thought to secrete a hypertonic primary fluid with a high K<super>+</super> concentration. This fluid is then modified by the ductal epithelia and transported to the avascular ocular surface. It is known that both sympathetic and parasympathetic input trigger protein release, but the role of adrenergic stimulation on water secretion in lacrimal gland remains unclear. Therefore, the first goal of this dissertation is to examine the influence ofΑ- andΒ-adrenergic activation on tear fluid production.Tear secretion requires coordination of different membrane channels and transporters. Walcott et al. showed the importance of basolateral Na<super>+</super>-K<super>+</super>-2Cl<super>-</super>-cotransporter (NKCC1) on secretion rate. The second goal is to develop an acinar cell mathematical model with cell volume regulation. The model is used to examine whether NKCC1 alone is sufficient to generate hypertonic tear fluid with high KCl content when the cell is stimulated. Subsequently the model was expanded with acid-base regulatory transporters to investigate the interaction between volume- and pH-regulation systems. This effort led to the discovery that the sodium-bicarbonate transporter is expressed in lacrimal gland and participates in tear production.Lastly, since acinar and duct cells express same membrane channels and transporters, it is likely that duct cells secrete a hypertonic fluid like acinar cell. The third goal of this project is to develop a duct cell model and combine it with the acinar cell model. The combined model was used to examine the flow dependence of tear composition. The predictions agree with measurements made in anesthetized rats.