Tears, the secretory product of the lacrimal gland, serve not only as a lubricant of the corneal surface but also as a primary defense against airborne antigens that contact the avascular cornea. The major anti-bacterial/viral agents in tears are the immunoglobulins secreted by plasma cells of the lacrimal gland. Elucidation of the physiology of the lacrimal glans at the cellular level is of critical importance to the amelioration of conditions such as """"""""dry eye."""""""" The major focus will be determination of the role membrane channels and receptor mediated messenger systems play in the modulation of immunoglobulin secretion. There is evidence to support the notion that plasma cells contain receptors responsive to neurotransmitters and that these same transmitters can alter antibody secretion by the lacrimal gland. The Harderian (lacrimal) gland of the chicken will be the system used because the gland has a very high density of plasma cells and the principle immunoglobulin secreted by the avian lacrimal gland is an IgG which is thought to diffuse passively and unmodified through the surrounding cortical epithelium (Mullock et al., 1981). This is distinctly different than the rat lacrimal gland where the secreted immunoglobulin (IgA) is dimerized and then secreted by the secretory epithelium (Peppard and Montgomery, 1987). The preliminary results indicate that there are receptor mediated mechanisms capable of modulating the secretory rate of IgG out of the lacrimal gland and that the receptors are housed within the membrane of the plasma cells of the gland. Electrophysiological data indicate that membrane potential (manipulated by maxi-K channel activity) is an intrinsic """"""""down"""""""" regulator of immunoglobulin secretion.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009406-03
Application #
2163034
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1992-01-01
Project End
1995-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Physiology
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Ding, Chuanqing; Walcott, Benjamin; Keyser, Kent T (2003) Sympathetic neural control of the mouse lacrimal gland. Invest Ophthalmol Vis Sci 44:1513-20
Sundermeier, Thomas; Matthews, Gary; Brink, Peter R et al. (2002) Calcium dependence of exocytosis in lacrimal gland acinar cells. Am J Physiol Cell Physiol 282:C360-5
Walcott, Benjamin; Moore, Leon C; Birzgalis, Aija et al. (2002) Role of gap junctions in fluid secretion of lacrimal glands. Am J Physiol Cell Physiol 282:C501-7
Paranyuk, Y; Claros, N; Birzgalis, A et al. (2001) Lacrimal gland fluid secretion and lymphocytic infiltration in the NZB/W mouse model of Sjogren's syndrome. Curr Eye Res 23:199-205
Ding, C; Walcott, B; Keyser, K T (2001) Neuronal nitric oxide synthase and the autonomic innervation of the mouse lacrimal gland. Invest Ophthalmol Vis Sci 42:2789-94
Goldfine, S M; Walcott, B; Brink, P R et al. (1999) Myocardial connexin43 expression in left ventricular hypertrophy resulting from aortic regurgitation. Cardiovasc Pathol 8:1-6
Walcott, B; Claros, N; Patel, A et al. (1998) Age-related decrease in innervation density of the lacrimal gland in mouse models of Sjogren's syndrome. Adv Exp Med Biol 438:917-23
Brink, P R; Peterson, E; Banach, K et al. (1998) Electrophysiological evidence for reduced water flow from lacrimal gland acinar epithelium of NZB/NFW F1 mice. Adv Exp Med Biol 438:209-19
Brink, P R; Walcott, B; Roemer, E et al. (1994) The role of membrane channels in IgG secretion by plasma cells in the chicken lacrimal gland. Adv Exp Med Biol 350:151-6
Brink, P R; Walcott, B; Roemer, E et al. (1994) Cholinergic modulation of immunoglobulin secretion from avian plasma cells: the role of calcium. J Neuroimmunol 51:113-21

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