NUCLEAR RETINOIC ACID RECEPTORS IN THE LACRIMAL GLAND

The lacrimal gland secretes and metabolizes retinoids and responds to retinoic acid in culture. Like other retinoid responsive organs it is expected to express the nuclear retinoid receptors. The goal of this s tudy was to identify the retinoic acid receptors (RAR) in the lacrimal glands of rats, rabbits, and humans. Total RNA was prepared from whol e lacrimal glands and rat lacrimal gland acinar cells grown in culture . RNA was subjected to Northern blot analysis and probed for the RAR a lpha, RAR beta, and RAR gamma mRNAs. Nuclear extracts of rat and rabbi t lacrimal glands were incubated with H-3-all-trans retinoic acid and analyzed by gel filtration chromatography Western blots of the nuclear extracts were probed using monoclonal antibodies to RAR alpha and RAR beta. Rat lacrimal gland expresses RAR alpha mRNA with two transcript s (3.8 and 3.0 kb), a single RAR beta mRNA transcript (3.3 kb), and a single RAR gamma mRNA transcript (3.3 kb). Cultured rat lacrimal acina r cells also expressed the mRNA for all three RAR subtypes. Rabbit lac rimal glands express mRNAs for RAR alpha (3.7 and 2.9 kb) and RAR beta (3.2 kb) but RAR gamma mRNA is not detectable. Human lacrimal glands also express mRNA for RAR alpha (3.5 and 2.3 kb), RAR beta (3.4 kb) an d RAR gamma (3.0 kb). Lacrimal gland nuclear extracts contain proteins in the 50 kDa range that specifically bind retinoic acid with K-d = 1 .25 nM in rat lacrimal gland and 0.3 nM in rabbit. The monoclonal anti bodies identified RAR alpha and RAR beta in both rat and rabbit lacrim al glands. The results of this study support a role for retinoids in m aintaining the structure and function of the lacrimal gland. The prese nce of RARs suggests potential interactions of these receptors with ot her members of their superfamily, including androgen and thyroid recep tors, which also may be involved in lacrimal function.