Retinal taurine concentrations

Cats fed a taurine-free, casein diet develop retinal taurine deficiency and subsequently photoreceptor cell death. (Berson, Hayes, Rabin, Schmidt, and Watson, 1976 Schmidt, Berson and Hayes, 1976 Schmidt, Berson, Watson and Huang, 1977). Supplementation of this diet with methionine, cysteine, inorganic sulfate, vitamin B., or vitamin B plus cysteine did not prevent development of retinal taurine deficiency and retinal malfunction. A synthetic amino acid diet devoid of casein and taurine also resulted in retinal taurine deficiency and retinal malfunction. Only taurine-containing diets (i.e., chow or casein plus taurine) preserved normal retinal taurine concentrations arid electroretinogram (ERG) amplitudes. These findings have firmly established a role for exogenous taurine in maintaining normal retinal function in the cat. 

In taurine-deficient cats the decreases in retinal taurine concentrations and reductions in ERG amplitudes have been closely correlated (Fig. 1). This correlation could be demonstrated prior to detectable cell death as measured by changes in retinal deoxyribonucleic acid (DNA) concentrations. Reductions in retinal taurine concentrations below 50% of normal were associated with the appearance of abnormal granularity in the area centralis and reduction in retinal DNA concentrations. At a time when retinal taurine concentrations were reduced 70-80% below normal, the ERG responses were small or non-detectable, and ultrastructural studies showed photoreceptor cell death (Hayes, Rabin and Berson, 1975). 

Figure 1. Peak-to-peak amplitudes and retinal DNA concentrations related to retinal taurine concentration in 10 control and 38 taurine-deficient cats. Controls were considered to have 100% retinal taurine concentration, ERG amplitude, and retinal DNA concentration. Taurine-deficient cats were divided into six groups of 4 to 8 according to the amount of taurine in their retinas. For each group, average amplitudes (mean + SEM) for rod (black dots) and cone (circles) responses and average DNA values (squares) are presented. The coefficients of correlation for rod ERG amplitude and cone ERG amplitude to retinal taurine concentration were 0.90 and 0.84 respectively. (Reproduced with permission from Schmidt, Berson,...

This suggests that in both species retinal taurine concentrations are maintained by uptake of taurine from the plasma and not by synthesis in situ in the retina. 

In contrast to the taurine-deficient cat in which retinal deficiency precedes photoreceptor cell death, decreases in retinal taurine concentrations in the RCS/p+ rat occur simultaneously with photoreceptor cell death after the third week of postnatal life. During early postnatal life, the RCS rat retina develops comparably to that of normal rats, and until about 21-23 postnatal days, the RCS rat retina is similar to normal with respect to the thickness of the outer nuclear layer, retinal DM and taurine concentrations, and ERG amplitudes. After the 23rd postnatal day, the photoreceptor cells begin to degenerate, and thereafter the reductions in retinal taurine content (Figure 5) can be correlated with reduction in the thickness of the outer nuclear layer, decrease in retinal DM concentrations, and a decline in ERG amplitudes. 

Figure 5. Retinal taurine concentrations, ERG amplitudes and retinal DNA concentrations at various postnatal ages in normal Long-Evans rats and pigmented RCS rats with hereditary retinal degeneration.

Studies with taurine-deficient cats have provided a new approach to the study of the cell biology of photoreceptor cells. The mechanism by which retinal taurine-deficiency leads to photoreceptor cell death remains to be defined. The close correlation of retinal taurine deficiency with peak-to-peak ERG amplitudes in taurine-deficient cats suggests that taurine deficiency may have some effect on the ionic fluxes of Na" " and K involved in the generation of the ERG. Since the generation of the ERG depends on hyperpolarization of photoreceptor cells and depolarization of Mtiller cells, it is possible th t taur. ne deficiency has led to abnormal ionic concentrations Na and K ) in photoreceptor and MUller cells. This possibility is currently under investigation. 

In a few studies it has been demonstrated that taurine supplementation improves retinal development in premature babies receiving parenteral nutrition. Human data on the efficacy of taurine supplementation in so-called energy drinks are very limited. In the absence of taurine supplementation in children taurine concentrations drop, suggesting its conditional indispensability also in the postneonatal period. This has led to the addition of taurine to standard feeding formulas for infants and growing children. 

A quantitatively important pathway of cysteine catabolism in animals is oxidation to cysteine sulfinate (Fig. 24-25, reaction z),450 a two-step hydroxyl-ation requiring 02, NADPH or NADH, and Fe2+. Cysteine sulfinic acid can be further oxidized to cyste-ic acid (cysteine sulfonate),454 which can be decarbox-ylated to taurine. The latter is a component of bile salts (Fig. 22-16) and is one of the most abundant free amino acids in human tissues 455-457 Its concentration is high in excitable tissues, and it may be a neurotransmitter (Chapter 30). Taurine may have a special function in retinal photoreceptor cells. It is an essential dietary amino acid for cats, who may die of heart failure in its absence,458 and under some conditions for humans.459 In many marine invertebrates, teleosts, and amphibians taurine serves as a regulator of osmotic pressure, its concentration decreasing in fresh water and increasing in salt water. A similar role has been suggested for taurine in mammalian hearts. A chronically low concentration of Na+ leads to increased taurine.460 Taurine can be reduced to isethionic acid... 

Taurine - A glyclne-like, sulphur containing amino acid, taurine (12) is found in reasonably high concentrations throughout the mammalian central nervous system and in heart.In brain, taurine is formed as a result of the decarboxylation of cysteine sulphinic acid (15) to hypotau-rlne (8 ), which in turn is oxidized to form taurine.Like other transmitter candidates, taurine is accumulated and released by brain tissue and the accumulation can be inhibited by ouabain. Clinically, significant alterations in taurine levels may be associated with retinitis pigmentosa, epilepsy, mongolism, and possibly heart disease. 

Those human infants fed the currently available synthetic formulas often have taurine-containing foods added to the diet within a few weeks or months of birth, and the time scale for induction of retinal degeneration in the cat is of the order of months. Furthermore, the concentration of taurine in retina of most species, although high, is not as great as in the retina of the cat. This high concentration of taurine may render the cat retina especially vulnerable. 

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