Retinitis pigmentosa, vitamin

Patients with abetalipoproteinaemia, a rare inborn disorder of lipoprotein metabolism, are totally deficient in vitamin E fiom birth and, if untreated, invariably develop a characteristic pigmentary retinopathy similar to that seen in retinitis pigmentosa and peroxisomal disorders. The same retinopathy has been observed in other patients with severe and chronic vitamin E deficiency. A essive vitamin E replacement therapy in all these patients has been shown either to prevent, to halt the progression of, or in some cases, to improve the characteristic visual abnormalities (Muller and Lloyd, 1982). 

Retention time, in chromatography, 6 374-375, 409-410 ( )-Reticuline, 2 90 Retina, 7 307-308 Retinal, 25 787. See also Vitamin A carotenes and, 25 790 Retinitis pigmentosa, 17 659 Retinoic acid, 25 787-789, 790. See also Vitamin A... 

ABL) recessive lipoproteins particle fat-soluble vitamin deficiencies, spinocerebellar disease, retinitis pigmentosa, acanthocytosis, galee blanche intestine, fatty liver apoB lipoproteins (chylomicrons, VLDL, and LDL)... 

This condition leads to permanent blindness in about half of cases, and many of those affected are preschool children. Night blindness occurs early in vitamin A deficiency. There is a reduction in rhodopsin concentration, followed by retinal degeneration and loss of photoreceptor cells. Degenerative changes may be due to instability of free opsin or may indicate an additional nutritive function for retinaldehyde (or retinoic acid) in retinal cells. The degenerative changes of retinitis pigmentosa, a relatively common, inherited cause of blindness, closely resemble those of vitamin A deficiency. 

Gouras P, Carr RE, Gunkel RD. 1971. Retinitis pigmentosa in abetalipoproteinemia Effects of vitamin A. Invest Ophthalmol Vis Sci 10 784-793. 

The current recommendation for retinitis pigmentosa is to administer 15,000 lU of vitamin A palmitate daily under the supervision of an ophthalmologist and to avoid high-dose vitamin E. 

What is the likelihood that retinitis pigmentosa is associated with a defect in the transport of vitamin A within the ocular tissues or in an enzyme responsible for its isomerization or conversion to one of its derivatives Some of the evidence against this view depends on comparisons between retinitis pigmentosa patients... 

What defects in vitamin A transport or utilization are likely to occur in the diseased eye The cytosol and IPM binding proteins and their possible receptors are clearly essential components of the visual system, as are the specific enzymes that are implicated at certain stages of the visual cycle (Table II). Failure to isomerize el -trans to Il-cu-retinoid is one obvious possibility, and a clinical trial was carried out by Chatzinoff et al. (1968) in an attempt to answer this question. The compound ll-c/5- vitamin A (the retinoid used was not reported) was injected intramuscularly into retinitis pigmentosa patients over a 3-year period. This group was then compared with a parallel group of patients that had received the all-trans isomer. No beneficial effect of 11-crr-retinoid was found. However, the ease with which the 11-cis isomer isomerizes back to all-trans when dispersed in tissue preparations (see Section III,G,4,b) casts doubt on the likelihood that in this study any 11-cM-retinol would have survived to be delivered to the RPE. 

The cause or causes of retinitis pigmentosa are yet to be found and at present a possible role for vitamin A in this condition has not been established. However, the above studies have enabled us to eliminate some possibilities and to identify others. The retinitis pigmentosa eye was normal in its ability to store retinoid, to esterify retinol, and to convert the all-trans isomer to 11-cis. A major abnormality was the absence of interstitial retinol-binding protein. It has not been established whether this is a selective loss, or whether other components of the interphotoreceptor matrix are also involved. Clearly, much more woric is needed before we arrive at an insight into the causes of chorioretinal binding diseases. 

The retinopathy may be related to vitamin A or carotenoid deficiency (Salt et al. 1960, and others), and low serum levels of vitamin A were found by Campbell and Tonks (1963) in other patients with retinitis pigmentosa. However, in the patient of Salt et al., normal serum levels of this vitamin were maintained from the age of 22 months by the administration of water-soluble vitamin A preparations and he nevertheless showed the first signs of retinitis pigmentosa at the age of 5 years (Wolff et al. 1966). Similarly Forsyth et al. (1965) administered vitamin A to their patients in daily doses of 20,000 to 40,000 lU, and achieved serum levels of 55 lU/lOOml (normal 72 lU/lOOml) but were unable to prevent the development of retinitis and the appearance of neurological signs at the age of 7. Even with normal serum levels of vitamin A, its transport to important sites may not be secured, and coupling with j8-lipoproteins may be necessary for its action. In addition, some cells may need carotenoids which are almost completely absent in the serum of a-j8-lipoproteinemic patients. 

Whether long-term administrations of water-soluble vitamin A preparations, which are customarily given in each case of retinitis pigmentosa, are of any benefit remains to be seen. As mentioned earlier, ingestion of vitamin A over years by some patients (Wolff et al. 1965/1966) with a-/8-lipoproteinemia, failed to prevent the development of retinitis pigmentosa and ataxia, in spite of satisfactory serum levels. Nevertheless, the fat soluble vitamins A, D and E, and possibly vitamin K in the presence of hypoprothrombinemia, should be substituted. The lack of plasma carotenoids persists in spite of these measures. 

Campbell, D. A., and E. L. Tones Biochemical findings in human retinitis pigmentosa with particular relation to vitamin A deficiency. Brit. J. Ophthal. 46, 151 (1962). 

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