Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5

The expression of three aquaporin (AQP)-type water channels has been report ed in the lacrimal gland: AQP5 in the apical membranes of acinar and duct c ells, AQP4 in the basolateral membranes of acinar cells, and AQP1 in microv ascular endothelia. Recent experiments indicate that water movement through AQP5 in the salivary grand is important in saliva secretion. To investigat e the role of aquaporins in lacrimal gland function, basal and pilocarpine- stimulated tear secretion was compared in wildtype mice and knockout mice l acking AQP1, AQP4 and AQP5, as well as AQP3, which was found here to be exp ressed in the basolateral membrane of acinar cells. Tear fluid was collecte d in anesthetized mice using microcapillary tubes before and at 4 min inter vals after pilocarpine administration. Tear fluid volumes were (in mu l per 4 min, S.E.): 0.69 +/- 0.06 (wildtype mice), 0.70 +/- 0.07 (AQP1 -/-), 0.8 1 +/- 0.13 (AQP3 -/-), 0.62 +/- 0.14 (AQP4 -/-), and 0.78 +/- 0.09 (AQP5 -/ -) (differences not significant). Chloride concentrations (average 155 +/- 13 mM) measured by a fluorescence assay were also not different in tear flu id collected from wildtype vs aquaporin null mice. These findings provide d irect evidence against an essential role for aquaporins in lacrimal gland f luid secretion, The requirement for aquaporins in salivary but not lacrimal gland secretion, may involve the substantially slower fluid secretion rate across lacrimal grand acinar cells. (C) 2000 Academic Press.