tain normal differentiation of the cornea and conjunctival membranes, thus preventing xerophthalmia (Sommer and West, 1996), as well as for the photoreceptor rod and cone cells of the retina. Rods contain the visual pigment rhodopsin (opsin protein bound to 11-cis-retinal). The absorption of light catalyzes the photoisomerization of rhodopsin’s 11-cis-retinal to all-trans-retinal in thousands of rods, which triggers the signaling to neuronal cells associated with the brain’s visual cortex. After photoisomerization, all-trans-retinal is released, and for vision to continue, 11-cis-retinal must be regenerated. Regeneration of 11-cis-retinal requires the reduction of all-trans retinal to retinol, transport of retinol from the photoreceptor cells (rods) to the retinal pigment epithelium, and esterification of all-trans-retinol, thereby providing a local storage pool of retinyl esters. When needed, retinyl esters are hydrolyzed and isomerized to form 11-cis-retinol, which is oxidized to 11-cis-retinal and transported back to the photoreceptor cells for recombination with opsin to begin another photo cycle.
Vitamin A is required for the integrity of epithelial cells throughout the body (Gudas et al., 1994). Retinoic acid, through the activation of retinoic acid (RAR) and retinoid X (RXR) receptors in the nucleus, regulates the expression of various genes that encode for structural proteins (e.g., skin keratins), enzymes (e.g., alcohol dehydrogenase), extracellular matrix proteins (e.g., laminin), and retinol binding proteins and receptors.
Retinoic acid plays an important role in embryonic development. Retinoic acid, as well as RAR, RXR, cellular retinol-binding protein (CRBP), and cellular retinoic acid-binding proteins (CRABP-I and CRABP-II), is present in temporally specific patterns in the embryonic regions known to be involved in the development of structures posterior to the hindbrain (e.g., the vertebrae and spinal cord) (Morriss-Kay and Sokolova, 1996). Retinoic acid is also involved in the development of the limbs, heart, eyes, and ears (Dickman and Smith, 1996; Hofmann and Eichele, 1994; McCaffery and Drager, 1995).
Retinoids are necessary for the maintenance of immune function, which depends on cell differentiation and proliferation in response to immune stimuli. Retinoic acid is important in maintaining an adequate level of circulating natural killer cells that have antiviral and anti-tumor activity (Zhao and Ross, 1995). Retinoic acid has been shown to increase phagocytic activity in murine macrophages (Katz et al., 1987) and to increase the production of interleukin 1 and other cytokines, which serve as important mediators of inflammation and stimulators of T and B lymphocyte production (Trechsel