The overall objective of the proposed work is to study the nutritive relationship of the tears to the cells of the ocular surface. It has recently been reported that retinol is present in tears. Since vitamin A may affect and be involved in the regulation and maturation of cells in the cornea and conjunctiva, the studies will initially focus on delivery of vitamin A to the ocular surface by the tears based on the hypothesis that ocular surface disease, especially keratinization, in patients with tear film abnormalities may in part be due to inadequate delivery of vitamin A to the ocular surface epithelium by the tears.
The specific aims of the project are to: 1) determine the source of retinol in the tears by high pressure liquid chromatography (HPLC) of secretions and extracts of the tear-producing glands and by radioautography of tear-producing glands after system treatment of animals with radiolabeled retinoids. 2) study the relationship of vitamin A in tears to the health of the ocular surface by comparing labeling of the cornea by systematically administered radiolabeled retinoids in normal animals and animals with impaired tear function, by attempting to reverse keratinization of corneas in animals with impaired tear function by topical application of retinoids, and by measuring retinol concentration by HPLC in tears of humans and animals with ocular surface disease. 3) study the mechanisms of action of vitamin A in the cornea, by studies of the effect of retinoids on growth of corneal cells in culture and in vivo, and by HPLC analysis of retinoid metabolism in the cornea by studies of the effect of topical retinoids on endothelial wound healing.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005640-03
Application #
3260917
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1985-09-30
Project End
1988-11-30
Budget Start
1987-09-30
Budget End
1988-11-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
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
Bernal, D L; Ubels, J L (1992) Retinyl ester hydrolysis in the rabbit lacrimal gland. Curr Eye Res 11:889-98
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

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