The major objective of this project is to clarify the mechanism by which all-trans vitamin A is isomerized to the 11-cis form during dark adaptation. Once the mechanism is known, the relationship of the isomerization reaction to various pathological conditions, such as retinitis pigmentosa in humans, can be probed. Our studies thus far have provided the following progress: 1) by use of high pressure liquid chromatography, physiologically important isomers of retinaldehyde, retinal oxime, retinol and retinyl ester have been separated and quantitated, and 2) the net coversion of all-trans to 11-cis vitamin A has been demonstrated in the bovine eye cup in vitro and in homogenates of the neural retina, but not in the retinal pigment epithelium.
Specific aims are: 1) to study the cellular site and nature of the all-trans: 11-cis isomerization of vitamin A in the eye, 2) to investigate a possible linkage between the isomerization reaction and energy donating systems, 3) to examine in detail the mechanism of the isomerization reaction, and 4) to probe the possible relationships between defects in isomerization and degenerative diseases of the retina. Our working hypothesis is that all-trans retinaldehyde, when bound to a specific binding protein in the rod cell or Muller cell, is isomerized to the 11-cis form in the presence of a suitable energy-donating system. It is then transferred, possibly via interstitial (interphotoreceptor) retinoid binding protein and/or some other yet unidentified binding protein, to opsin in the rod outer segment.
|Shi, H L; Furr, H C; Olson, J A (1991) Retinoids and carotenoids in bovine pineal gland. Brain Res Bull 26:235-9|
|Shi, H L; Olson, J A (1990) Site of conversion of endogenous all-trans-retinoids to 11-cis-retinoids in the bovine eye. Biochim Biophys Acta 1035:1-5|
|Landers, G M (1990) High-performance liquid chromatography of retinoid isomers. Methods Enzymol 189:70-80|
|Landers, G M; Olson, J A (1988) Rapid, simultaneous determination of isomers of retinal, retinal oxime and retinol by high-performance liquid chromatography. J Chromatogr 438:383-92|
|Olson, J A (1986) Some thoughts on the relationship between vitamin A and cancer. Adv Exp Med Biol 206:379-98|
|Landers, G M; Olson, J A (1986) Absence of isomerization of retinyl palmitate, retinol, and retinal in chlorinated and nonchlorinated solvents under gold light. J Assoc Off Anal Chem 69:50-5|
|Olson, J A (1986) Metabolism of vitamin A. Biochem Soc Trans 14:928-30|
|Barua, A B; Olson, J A (1985) Preparation of retinamides by use of retinoyl fluoride. J Lipid Res 26:258-62|