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.
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