The distribution and possible functions of ascorbic acid in the eye

Heath, Harold

doi:10.1016/s0014-4835(62)80025-6

Cited by 98 publications

(27 citation statements)

References 28 publications

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“…precursor sugar in senescent lenses. On the other hand, several reports point to the presence of ascorbate in millimolar concentrations in the human lens and to its high tendency to undergo browning and induce crosslinking when it reacts with proteins (13,24,25). These considerations and our data showing that ascorbate and its oxidation products can serve as pentosidine precursors strongly suggest that ascorbate is the major pentosidine precursor in the aging human lens.…”

Section: Resultssupporting

confidence: 62%

High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis.

Nagaraj

Sell

Prabhakaram

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

232

144

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Pentosidine is a recently discovered protein crosslink, involving lysine and arginine residues linked together in an imidazo [4,5,6] pyridinium ring formed by a 5-carbon sugar during nonenzymatic browning (Maillard reaction). The presence of high ascorbate levels in the human lens and its ability to undergo nonenzymatic browning led us to investigate pentosidine formation in the aging human lens. Incubation of lens crystallins with ascorbate and its oxidation products dehydroascorbate and 2,3-diketogulonate leads progressively to the formation of pentosidine crosslinks in the presence of oxygen. Under nitrogen, however, pentosidine forms only from 2,3-diketogulonate or xylosone, a degradation product of 2,3-diketogulonate. A high correlation between pentosidine crosslinks and the degree of lens pigmentation is noted in cataractous lenses. Pentosidine is found to be primarily associated with a-crystallin fractions of 300-5000 kDa. These results suggest that redox imbalance in cellular senescent systems such as the ocular lens may lead to irreversible ascorbate oxidation and protein crosslinking by xylosone. This mechanism may play an important role in the pathogenesis of "brunescent" cataracts.

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Section: Resultssupporting

confidence: 62%

High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis.

Nagaraj

Sell

Prabhakaram

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

232

144

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“…The most significant of these appears to be the glutathione system in conjunction with glutathione peroxidase, superoxide dismutase, and ascorbic acid (12). In mammals, ascorbate is present in the lens in unusually high concentration, as much as [30][31][32][33][34][35] times the blood level; in man, the lens ascorbate concentration is even greater than the already high level present in the aqueous humor (13,14). However, little is known about the role of ascorbic acid in lens function and in cataractogenesis.…”

mentioning

confidence: 99%

The role of ascorbic acid in senile cataract.

Bensch¹,

Fleming²,

Lohmann³

1985

Proc. Natl. Acad. Sci. U.S.A.

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The reductone ascorbic acid, present in the crystalline lens in concentrations higher than those of glucose, is capable of undergoing nonenzymatic "browning" in the presence of lenticular proteins. We studied the nonenzymatic browning with ascorbate in model systems employing bovine serum albumin and lens crystailins. When bovine serum albumin, a-crystallin, or y-crystallin was incubated with[14C]ascorbic acid, the formation of yellow and then brown condensation products appeared to correlate with increasing protein-associated radioactivity. The fluorescence spectrum of these products was similar to that of homogenates of human cataractous lenses. We suggest that the nonenzymatic reaction of lens crystallins with ascorbic acid may contribute, at least in part, to the color changes of aging lenses and to the physical lenticular deterioration leading to senile cataract. High dietary intake of ascorbic acid did not affect the fluorescence spectrum of murine lenses; thus, we assume that the speed and extent of the lenticular browning reactions must depend on a deterioration of other factors of the multicomponent antioxidant system of the eye.Senescent cataract is a very common spontaneous eye affliction in persons beyond middle age. It becomes progressively more severe and frequent in the elderly, with more than 85% of octagenarians having some degree of lenticular opacification (1). Of particular interest to us is the most common type of senescent cataract, the so-called nuclear sclerosis, in which the central portion of the lens undergoes a gradual increase in density and opacity, usually accompanied by a yellow to dark-brown discoloration (2). What prompted us to undertake these studies was the striking similarity in the appearance of such lenses with the color changes that develop during slow spontaneous autoxidation of ascorbic acid solutions, either in the presence or the absence of proteins. We here report observations on oxidative ascorbic acid-protein interactions in vitro. Comparison of our findings with data on cataractous lenses suggests that the biochemical reactions observed by us may play a role in the aging of human lenses. MATERIALS AND METHODSAll reactions were carried out in 67 mM potassium phosphate buffer (pH 7.4). Sterile solutions of ascorbic acid (Sigma) and proteins (bovine serum albumin, bovine lens a-crystallin, and bovine lens y-crystallin) were incubated for various times up to 1 month for, fluorescence studies, both at room temperature and at 370C. Bovine serum albumin was obtained (Sigma) as Cohn fraction V, essentially fatty acid-free. Lens crystallins were a gift from T. Chiou (National Taiwan University, Institute of Biochemical Sciences, Taipei, Taiwan). Sterility of the incubation mixtures was monitored periodically by testing aliquots on nutrient agar plates. The fluorescence spectra of these incubation mixtures were obtained with an Aminco Bowman spectrophotofluorometer model 4-8106 after prolonged dialysis of the ascorbic acid-containing protein solutions against lar...

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“…According to data of Dische and ZH [1951] the concentra tion of the reducer in normal human lenses: glutathione 170-180 mg/100 g, while ascorbic acid 30 mg/100 g [Heath, 1962] so it can be supposed that the reduction of the spin probe is caused by the glutathione in the lens.…”

Section: Resultsmentioning

confidence: 99%

Investigations on Normal and Cataractous Human Lenses by EPR

1979

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Normal and senile cataractous human lenses were studied by spin probe electron paramagnetic resonance (EPR) technique analyzing the reduction of added stable organic-free radicals. It has been concluded that the radical reduction kinetics were different at the different states of the senile cataract, and the conformational changes in lenticular proteins induced by the urea had no influence on the kinetics of the radical reduction. It is supposed that the decrease of the reduced glutathione is an exceedingly sensitive indicator of the change in the lens metabolism in the course of cataractous progression.

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The distribution and possible functions of ascorbic acid in the eye

Cited by 98 publications

References 28 publications

High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis.

High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis.

The role of ascorbic acid in senile cataract.

Investigations on Normal and Cataractous Human Lenses by EPR

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