Retinoids are secreted by the lacrimal gland. The proposed studies will test the hypothesis that the lacrimal gland is a specialized target tissue for Vitamin A which contains retinoid receptor proteins, enzymes for synthesis and hydrolysis of retinyl esters. and mechanisms for secretion of retinol into lacrimal gland fluid (LGF). It is proposed that a carrier protein in LGF, synthesized by the gland, transports retinol to the cells of the ocular surface, serving as a source of vitamin A for these cells.
Specific Aims : 1. Storage, synthesis, and hydrolysis of retinyl esters in the lacrimal gland will be studied by radioautography and measurement of acyl-CoA:retinol transferase activity and retinyl ester hydrolase activity. 2. Mechanisms and control of retinoid secretion will be studied in vitro using dispersed lacrimal gland acini and cultured cells. 3. It will be determined whether a 20-kd protein in LGF which binds retinol is retinol binding protein (RBP) by cloning the cDNA for this protein and probing the gland for RBP mRNA. 4. It will be determined whether cellular retinol and retinoic acid binding proteins are present in lacrimal gland by probing the gland for their messenger RNAs. 5. It will be determined whether the tears are a source of vitamin A for the cornea by measuring retinoid levels in corneas of rabbits with normal or impaired tear secretion. 6. Mechanisms of action of retinoids in the cultured corneal epithelial cells will be tested by measuring cAMP-dependent Protein kinase activity, laminin synthesis, and cell adhesion. These studies will contribute to the understanding of the relationship of tear film abnormalities to ocular surface disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005640-08
Application #
3260920
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-07-01
Project End
1993-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Eye and Ear Institute of Pittsburgh
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Ubels, John L (2005) A retrospective on topical retinoids occasioned by observation of unexpected interactions of retinoic acid with androgens and glucocorticoids in immortalized lacrimal acinar cells. Exp Eye Res 80:281-4
Ubels, John L; Veenstra, Eric; Ditlev, Jonathon et al. (2003) Interactions of testosterone and all-trans retinoic acid in regulation of androgen receptor expression in rat lacrimal gland. Exp Eye Res 77:741-8
Aupperlee, Mark D; Wertz, John T; Ingersoll, Kyle E et al. (2002) Identification of androgen receptors in rabbit lacrimal gland by immunohistochemsitry. Adv Exp Med Biol 506:137-41
Ubels, John L; Wertz, John T; Ingersoll, Kyle E et al. (2002) Down-regulation of androgen receptor expression and inhibition of lacrimal gland cell proliferation by retinoic acid. Exp Eye Res 75:561-71
Saarloos, M N; Husa, M R; Jackson 2nd, R S et al. (1999) Intermediate filament, laminin and integrin expression in lacrimal gland acinar cells: comparison of an immortalized cell line to primary cells, and their response to retinoic acid. Curr Eye Res 19:439-49
Ubels, J L; Dennis, M; Lantz, W (1994) The influence of retinoic acid on growth and morphology of rat exorbital lacrimal gland acinar cells in culture. Curr Eye Res 13:441-9
Ubels, J L; Harkema, J R (1994) The rabbit lacrimal gland in vitamin A deficiency. Invest Ophthalmol Vis Sci 35:1249-53
Perkovich, C L; Ubels, J L; Lee, S Y et al. (1993) Cellular retinol-binding protein and cellular retinoic acid-binding protein in the lacrimal gland. Exp Eye Res 56:513-9
Lopez Bernal, D; Ubels, J L (1992) Bile salt-independent retinyl ester hydrolase in the rat lacrimal gland. Int J Vitam Nutr Res 62:186-90
Lee, S Y; Ubels, J L; Soprano, D R (1992) The lacrimal gland synthesizes retinol-binding protein. Exp Eye Res 55:163-71

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