Abstract
Purpose: :
We have found that inflammatory lacrimal gland (LG) disease and pregnancy have opposite effects on LG immunoarchitecture, but the basal fluid production rate decreases in both states. However, while the ability to produce fluid in response to secretagogue stimulation decreases in rabbits with dacryoadenitis, it increases markedly in pregnant rabbits. Therefore we examined the influences of pregnancy and induced autoimmune dacryoadenitis (IAD) on expression of mRNAs for ion transporters and aquaporins (AQP) that mediate LG fluid secretion.
Methods: :
OS and OD LGs were obtained from 8 term pregnant rabbits (29 days gestation); 4 female rabbits with IAD autoadoptively transferred by ex vivo-activated lymphocytes; and 8 age- and season-matched female controls. mRNA was extracted from samples of each LG. Abundances of mRNAs for GAPDH, Na-K-2Cl co-transporter-1 (NKCC1), Na-H exchanger-1 (NHE1), Na-K-ATPase 1-subunit (NKA1), AQP4, and AQP5 were determined by real time RT-PCR with species-specific primer and probe sets.
Results: :
mRNAs for AQP4, NKCC1, and NKA1 were equally abundant in control and pregnant rabbits; while AQP5 decreased 22%, NHE1 increased 30%. In contrast, all mRNAs decreased (P ≤ 0.01) in rabbits with IAD: AQP4 ↓ 34%; AQP5 ↓ 53%; NKCC1 ↓ 65%; NKA1 ↓ 29%; and NHE1 ↓ 41%.
Conclusions: :
The large decreases of mRNAs for AQP4, AQP5, NKCC1, NKA1, and NHE1 in rabbits with IAD indicates that multiple molecular effectors of LG fluid production are down-regulated in this model of inflammatory LG disease. The decrease of AQP5 during pregnancy is consistent with our finding that basal LG fluid production decreases, but it suggests that AQP5 is not rate-limiting for stimulated LG fluid production. The increase of NHE1 abundance during pregnancy accords well with our finding that secretagogue-induced LG fluid production increases; it also suggests that the proportion of NHE that are quiescent in the absence of secretagogue stimulation increases during pregnancy.
Keywords: lacrimal gland • cornea: tears/tear film/dry eye • gene/expression