Retinol-binding protein (RBP) and pigmentary dystrophy of the retina.

Vitamin A (retinol) is a fat-soluble alcohol and is derived in the upper part of the small intestine from carotenoid plant pigments and Vitamin A esters present in food (Olson, I964). The free retinol then penetrates through the mucosal cells, perhaps aided by its polar or hydrophilic hydroxy group, and is re-esterified during transit (Glover and Walker, I 964). After absorption it reaches the liver, where it is stored chiefly as palmitate (Moore, I964), and whence it is slowly released into the circulation as free retinol (McLaren, 1970) and combines immediately with a specific transport protein, called retinol-binding protein (Kanai, Raz, and Goodman, i968), to form a protein-retinol complex (i.e. RBPretinol). One molecule of retinol binds to one molecule of RBP. The molecular complex makes the water-insoluble retinol become soluble and also protects the vitamin against degradation. Retinol-binding protein is a low molecular weight protein (mol. wt. 2 I,000) and escapes from the general circulation into the cerebrospinal fluid, the urine, and other tissue fluids (Peterson and Berggard, I 97 ). It therefore seems imperative that, in order to prevent an excessive loss ofVitamin A, the RBP-retinol complex should be further attached to a high molecular weight protein. It has recently been reported that the RBP-retinol complex is further attached to serum pre-albumin (PA) of mol. wt. 64,ooo. The complex thus formed is a protein-proteinretinol complex (i.e. PA-RBP-retinol) and has a mol. wt. of 85,000. Pre-albumin stabilizes the RBP-retinol complex and also serves an important physiological function by preventing glomerular filtration of the relatively small RBP molecule and hence loss of Vitamin A in the urine (Raz and Goodman, I969). After reaching the target organ, RBP dissociates from pre-albumin; Vitamin A is then released and the retinol-binding protein escapes into the urine (Peterson, I971). The ocular effects of (Vitamin A-deficient) purified rations were first noted by Osborne and Mendel (I 914), but it was McCollum and Simmonds (I 9 I 7) who recognized the missing factor and called it "Fat-Soluble A", which was later renamed Vitamin A. It is now known that Vitamin A is concerned in various metabolic and physiological functions; for example scotopic vision, sulphur metabolism (i.e. activation of sulphate for mucopolysaccharide production), steroid hormone production, and membrane stability (McLaren, I970). It has been suggested that protein deficiency impairs transport of Vitamin A to the tissue (Arroyave, Wilson, Mendez, Behar, and Scrimshaw, I961). It is possible that this impairment is due to a deficiency in the transport protein.