Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinicopathological studies were performed on 156 lenses of human senile cataract obtained by cataract operations between 1970 and 1988. It became clear that the aging influences the functional destruction of the equatorial region, the pathological changes of the bow area, and changes of the extralens environment. After operation for the atrophic type of the posterior subcapsular cataract, aftercataract easily develops on the intraocular lens and this requires treatment. Long-term observations were carried out in 180 Wistar male rats under the same laboratory condition and histological studies were performed. The similarities between the senile Wistar rat cataract and the human senile cataract indicate that the Wistar rat cataract is useful as a model for studying the human senile cataract. These rats were initially classified into six groups (control, vitamin E diet, EPC eye drops, catalin eye drops and reduced catalin eye drops). To study the effects of the agents (vitamin E, ARI, EPC, catalin, reduced catalin) on the cataract in senile Wistar rats the mean cell density of lens epithelia were measured at 2 or 3-month intervals. There were no statistically significant differences in treated groups and the control group. The results suggest that these agents affect another factor of lens apart from the proliferative activity of lens epithelial cell. Effects of anti-cataract agents were investigated using cultured lens epithelial cells. When cultured rat lens epithelial cells were incubated in medium containing selenite, super-oxide dismutase (SOD) activity and GSH in the cells markedly decreased, and GSSG was markedly increased. When cultured rabbit lens epithelial cells were incubated in medium contained selenite and glutathione, SOD activity was maintained normal level. When cultured lens epithelial cells were incubated in medium contained selenite and pirenoxin, SOD activity also maintained a normal level. These results suggest that both glutathione and pirenoxin are effective as anti-cataract agents. Cataracts in spontaneously hypertensive rats (SHR) was investigated on male of Wistar-Kyoto rats (WKY), stroke resistant SHR (SHRSR) and stroke-prone SHR (SHRSP) rats aged 3 to 9 months. Cataracts in these rats were classified as follows: Type 0: no opaciiy, Type 1: nuclear opacity, Type 2: posterior subcapsular opacity, Type 3: nuclear opacity associated posterior subcapsular opacity and Type 4: complete opacity in both lenses. Incidence of cataract in WKY was 2.6%, SHRSR, 76.8% ant SHRSP, 88.2%. Incidence of nuclear opacity was remarkably higher in SHRSP (48.5%). In SHR aged from 3 to 5 months, nuclear opacity was ahead of the appearance of posterior subcapsular opacity which was increased during aging.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cataract--clinic and pathology]. 227 35

Protein-thiol mixed disulfides in lenses have been implicated in the mechanism of protein-protein disulfide and other cross-linking leading to protein aggregation. The methodology for the detection and quantitation of protein-thiol mixed disulfides has been successfully established in our laboratory. Examination of mixed disulfides at different stages during development of a cataract may give relevant information on the mechanism of cataractogenesis, and whether oxidation is a part of that mechanism. In this study we investigated the involvement of mixed disulfides in cataract formation by using the H2O2-exposed lens as a model. Rat lenses, after being exposed to 0.5 mM H2O2 in culture showed an inverse relationship between the GSH loss and the protein-GSH formation with no effect on the protein-cysteine level. The H2O2-induced protein modification was also demonstrated indirectly by isoelectric focusing. The rate of protein-GSH production is dependent on the time of exposure and the concentration of H2O2. Age also plays some role as the lens GSH level decreases and the protein-thiol mixed disulfides increase as the animal becomes older. Lenses of older rats did not display more susceptibility to H2O2-induced mixed disulfide formation. The two protein-thiol mixed disulfides have a well-defined pattern of distribution in the rat lens. Most of the protein-GSH was found in the cortex and the water-soluble protein fraction whereas more protein-cysteine was found in the nucleus and water-insoluble protein fraction. Lens of older rat has more protein-cysteine as well as more water-insoluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of protein-thiol mixed disulfides in cataractogenesis. 237 74

When 0.25 mumol of hydrocortisone succinate sodium (HC) was administered to 15-day-old fertile eggs, almost all lenses of chick embryos treated with HC for 48 hr were classified as cataract stage IV-V (95%). A triple application of potassium pyrroloquinoline quinone (PQQ) (1.25 mumol/egg) at 3, 10 and 20 hr after HC treatment showed a preventive effect against the HC-induced cataract formation (I:45%, II:25%, III: 30%). PQQ also prevented the decline of GSH in the lens caused by HC. The decline of GSH in liver 24 hr after HC administration was prevented by PQQ. These data indicate that PQQ can modify HC-induced effects and that the preventive effect of PQQ against HC-induced decline of hepatic GSH seemed to influence HC-induced events in lens.
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PMID:Preventive effects of pyrroloquinoline quinone on formation of cataract and decline of lenticular and hepatic glutathione of developing chick embryo after glucocorticoid treatment. 254 18

Fluorescence of intact lenses of F1 (CBA x C57BL6) mice at different stages of X-ray cataract induced by gamma irradiation (5.00 Gr) has been studied by synchronous scanning of fluorescence, the shift between emission and excitation wave lengths being 20 nm. The ratio between peek intensities of the nontryptophan and tryptophan fluorescence within the synchronous scanning spectra (K) has increased 3.5 times as much at the stage of singular dot-like opacities. K-parameter correlated with GSH level in the lenses (r = -0.9). According to the results achieved, K could be regarded as an informative indicator of the development of X-ray cataract at the stage previous to turbidity.
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PMID:[The fluorescence of mouse crystalline lenses at different stages of radiation cataract studied by synchronous scanning]. 265 53

The polycyclic aromatic hydrocarbon naphthalene is bioactivated by cytochromes P450 to an electrophilic epoxide intermediate, which subsequently is metabolized to naphthoquinones (NQ) and possibly to a free radical intermediate. These reactive intermediates may bind covalently to lenticular tissues, cause oxidant stress and/or lipid peroxidation, thereby initiating cataracts. To evaluate this hypothesis, male C57BL/6 or DBA/2 mice were treated with naphthalene or one of several naphthoquinone and naphthol metabolites, in the presence or absence of modulators of chemical bioactivation and detoxification. In C57BL/6 mice, cataracts were caused by naphthalene (500-2000 mg/kg ip) in a dose-dependent fashion. The incidence of naphthalene-induced cataracts was decreased by pretreatment with the P450 inhibitors SKF 525A and metyrapone, the antioxidants caffeic acid and vitamin E, the glutathione (GSH) precursor N-acetylcysteine, and the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (p less than 0.05). Naphthalene cataractogenicity was enhanced by pretreatment with the cytochrome P450 inducer phenobarbital and the GSH depletor diethyl maleate (DEM) (p less than 0.05), and was unaffected by pretreatment with the prostaglandin synthetase inhibitors aspirin or naproxen, or the epoxide hydrolase inhibitor trichloropropene oxide. Cataracts were initiated by 1,2-NQ and 1,4-NQ (5-250 mg/kg ip) in a dose-dependent fashion, with a molar potency about 10-fold higher than that for naphthalene. NQ cataractogenicity was enhanced by pretreatment with DEM (p less than 0.05). 1-Naphthol (56 to 562 mg/kg ip) demonstrated a cataractogenic potency intermediary to that for naphthalene and NQ. DBA/2 mice treated with naphthalene (2000 mg/kg ip), 1,4-NQ (65-250 mg/kg ip), 1,2-NQ (30-250 mg/kg ip), or DEM followed by 1,4-NQ (125 mg/kg ip) did not develop cataracts. These results suggest that naphthalene cataractogenesis in C57BL/6 mice requires P450-catalyzed bioactivation to a reactive intermediate, which may be the NQ and/or a free radical derivative, either of which is dependent upon GSH for detoxification.
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PMID:In vivo murine studies on the biochemical mechanism of naphthalene cataractogenesis. 274 33

The effect of vitamin E-containing liposome on experimental sugar cataract formation in vitro was investigated. The lenses of male Wistar rats aged 6 weeks were prepared by incubating with 55. 6 mM glucose with vitamin E-containing liposome (dipalmitoyl phosphatidylcholine: DPPC). We examined the formation of lens opacity and assayed vitamin E and its related compounds. Incubation with vitamin E-containing liposome prevented sugar cataract formation. In Addition, vitamin E concentration in lens was significantly elevated by incubation with vitamin E-containing liposome. In lenses of the high level glucose group incubated without vitamin E-containing liposome, lipid peroxide (LPO) content was increased, but in lenses of the high-level glucose group incubated with vitamin E-containing liposome the increase was significantly inhibited at each incubation time. Vitamin E had no effect either on the decrease of reduced glutathione (GSH) or the increase of sorbitol content in lens incubated with high level glucose medium. In conclusion vitamin E-containing liposome was transported from medium to lens well and was significantly effective in preventing experimental sugar cataract formation in vitro. The protective effects of vitamin E are probably caused not only by its antioxidative action.
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PMID:[Effect of vitamin E-containing liposome on experimental sugar cataract]. 275 Jun 6

The ability of 2,6-dimethoxyquinone (DMQ) to impair 86Rb uptake by bovine lens epithelial cells was found to be independent of exogenous ascorbate in contrast to the impairment induced by Fe/Cu or riboflavin plus light. The cytotoxicity was associated with an electron spin resonance (ESR) detectable singlet radical (g = 2.0062) which also formed on incubation of DMQ with glutathione (GSH) or gamma-crystallin in vitro. Formation of the stable free radical appeared to require conjugation of DMQ by peptidyl thiol and required transition metal catalysis. A structure for the DMQ-glutathione free radical conjugate is proposed. Redox activity of quinone conjugates is suggested to be of relevance to an oxidative damage hypothesis of cataract.
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PMID:Pro-oxidant activation of ocular reductants. 2. Lens epithelial cell cytotoxicity of a dietary quinone is associated with a stable free radical formed with glutathione in vitro. 282 94

Selenium toxicity was investigated in cultured rabbit lenses to provide further information about the role of Ca++ in Se cataract. At a dose of 0.1 mM for 20 hr, Se induces a 10% change in Na levels within 6 hr, a 30% increase after 20 hr, and a three-fold increase within 48 hr of subsequent culture after removal of Se. In contrast, Ca++ levels remained normal throughout the first 24 hr. Only a small, 25% decline in GSH was noted. Not until lenses begin to swell and become noticeably opaque and turbid were Ca++ levels found to be elevated. Thus, at 72 hr, 48 hr following the removal of selenium, Ca++ had increased to a concentration of 0.7 mM. Ca++ accumulation appears to be a consequence of osmotic stress rather than pump inhibition while Na accumulation is a direct consequence of Se-inhibited Na pump.
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PMID:Effects of selenium on ion homeostasis and transparency in cultured lenses. 291 10

This study focused on whether changes in lens levels of glutathione and calcium, early events associated with cataract formation, were related or that one might cause the other. The first part of the investigation was concerned with the extent to which an increase in levels of intracellular calcium might alter GSH levels in lens fiber and epithelial cells. The results demonstrate that calcium accumulation, either at 19 degrees C or 37 degrees C, did not diminish the concentration of GSH. More importantly, GSH levels did not decline in opaque regions of a calcium-loaded lens. The reciprocal part of the problem focused on whether a decline in lens thiol might lead to an increase in levels of calcium and subsequent opacification. In particular, it was shown that treatment of lenses with parachloromercuribenzene sulphonic acid (PCMBS), a nonpenetrating sulphydryl probe, resulted in a 10-30% loss of membrane SH groups in the epithelium. Diminished numbers of SH groups was accompanied by chloride fluxes and an increase in membrane permeability to sodium and calcium with an influx of sodium and calcium leading to opacities. It is important to note that these changes occurred in the absence of any change in cellular levels of soluble protein-SH or GSH. Additional experiments suggest that calcium transport was not impaired, as evidenced by lack of inhibition of Ca-ATPase activity in lenses treated with PCMBS. The results suggest that one explanation for opacification is that oxidative insults, which diminish GSH levels, leads to a loss of important membrane SH groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The importance of membrane sulfhydryl groups to calcium homeostasis in the lens. 299 53

The response of the poikilothermal lens to various incubation temperatures in vitro was compared with that of the homothermal lens. The rainbow trout lens was used as the poikilothermal lens and the rat lens as the homothermal lens. In contrast to rat lenses, cataract developed at 37 degrees C in rainbow trout lenses, which was called 'warm cataract'. Warm cataract developed not only when lenses were incubated in vitro but also when rainbow trout were kept in water at 37 degrees C. Water, Na+, Ca2+ and insoluble protein increased and K+ and Mg2+ decreased in warm cataract lenses, but GSH and soluble protein sulfhydryl levels did not change. This cataract was irreversible after only 5 min incubation at 37 degrees C. On the other hand, rainbow trout lenses remained transparent without the change of cation balance at 0-25 degrees C while cold cataract developed in rat lenses. Na,K-ATPase activity was detected at 0 degrees C in rainbow trout lens homogenates, but not in rat lens homogenates. Na+-K+ ratio (Na+/K+) increased when the rainbow trout lens was treated with ouabain at 0 degrees C. In the rainbow trout lens, lactic acid was produced continuously for 30 days at 0 degrees C while it was not in the rat lens between 1 hr and 10 days after. These results strongly suggest that Na,K-ATPase acts as a cation pump at 0 degrees C and that ATP is supplied by glycolysis in the rainbow trout lens in order to maintain the transparency. The above results also suggest that enzymes and membrane structures in rainbow trout lens are adapted to a cold-temperature habitat and that Na,K-ATPase and anaerobic glycolysis are important for the maintenance of lens transparency at low temperatures.
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PMID:Studies on the eye lens in poikilothermal animals. I. Comparative studies on cation maintenance systems in rainbow trout and rat lenses. 299 50


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