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)

L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, was administered four times daily to mouse pups on post-natal days 7 and 8, inducing initiation of opacification on day 9. The initial progression of the cataract (less than 24 hr) was divided into four stages: (1) developing floriform; (2) mature floriform; (3) degenerate floriform; and (4) amorphous translucent cataract. Following this, dense corticonuclear opacities developed within several days. Two-dimensional gel electrophoresis of water-soluble whole lens extracts indicated that the most rapid early cataractous changes, occurring mainly during stage 2, were loss of the two major components of the heavy beta-crystallin fraction, a 31-kDa basic polypeptide and an acidic component at 27 kDa, concomitant with the appearance of new species at 30 and 25 kDa. This was followed by more extensive modification of both alpha and beta-crystallins during stages 3 and 4 and the appearance of abnormal species at 26, 19 and 18 kDa, which were slightly more acidic than the major normal alpha A-crystallin polypeptide. The gamma-crystallin components, relatively unaffected at stage 4, were then lost rapidly as dense opacities ensued. By contrast with the water-soluble fraction, the normal day 9 urea-soluble fraction was deficient in gamma-crystallin polypeptides and enriched in anodic components whose relative electrophoretic mobilities were similar to those reported previously for phosphorylated bovine alpha A-crystallin and several cytoskeletal polypeptides. At stage 4 of the cataract, the modifications of normal alpha and beta-crystallin components in the urea-soluble fraction paralleled those in the water-soluble fraction, but the products seen were more numerous. In addition, the cytoskeletal proteins were no longer detectable. Substantial increases in lens Ca2+ that precede all of the above changes in lens polypeptide composition suggest that Ca(2+)-activated proteolysis may play a major role in development of BSO cataracts.
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PMID:Progressive modifications of mouse lens crystallins in cataracts induced by buthionine sulfoximine. 162 46

Cataracts were induced in suckling mice by multiple injections of L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, starting on post-natal day 7. The earliest visible lens aberrations began approximately 2 days after t(o), following 99% depletion of lens GSH. Cataract development then proceeded through four stages within less than 24 hr. Elevated Na+ and Ca+ and decreased K+ were first detected in pre-cataractous (stage 0) lenses. During stage 0, lens Na+ and K+ levels displayed a significant inverse correlation; by contrast, Ca2+ levels were poorly correlated with those of Na+. The initial increase in Na+ exceeded the decrease in K+. This suggested the presence of osmotic stress prior to cataract stage 1 (developing floriform). Increased lens hydration was first apparent in stage 1, coincident with a marked elevation of Ca2+, further increase in Na+ and decrease in K+. These trends persisted in the stage 2 cataract (completed floriform). Subsequent changes in lens hydration and cation content during cataract stages 3 (degenerate floriform) and 4 (amorphous translucent) suggested substantial influx of extracellular fluid into the affected lenses. The BSO cataract may represent a useful in vivo model to study the functions of GSH in maintaining normal lens cation balance and transparency.
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PMID:Lens GSH depletion and electrolyte changes preceding cataracts induced by buthionine sulfoximine in suckling mice. 162 47

Addition of calpain II (EC 3.4.22.17) to soluble proteins from 10-day-old rat lens caused an increase in turbidity and production of water-insoluble protein. The insolubilization increased with higher concentrations of both lens protein and calpain II, it could be prevented by the cysteine protease inhibitor E-64; it required at least 0.5 mM Ca2+, it was limited to 6% of the soluble protein present and resulted from precipitation of proteolyzed beta-crystallin polypeptides. When compared by two-dimensional electrophoresis, the insoluble beta-crystallin polypeptides produced by calpain II were similar to insoluble beta-crystallin polypeptides found in cataractous lenses. Trypsin also caused insolubilization of beta-crystallin polypeptides, but these polypeptides were unlike polypeptides produced during cataract formation. These data suggested that the loss of solubility was due to a specific removal of N/or C-terminal extensions from beta-crystallin polypeptides by calpain II, and that a similar process may occur in vivo during cataract formation. It is hypothesized that the insoluble protein produced by calpain II causes cataract by increasing light scatter in the lens.
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PMID:Calpain II induced insolubilization of lens beta-crystallin polypeptides may induce cataract. 162 59

Lenses cultured in diamide first developed outer cortical opacities followed by nuclear cataract. Lens hydration and total calcium were markedly increased by diamide. Proteolysis of crystallins were observed in nuclear cataract lenses. Calpain in the soluble fraction of lenses cultured with diamide was decreased, while calpain in the insoluble fraction was increased. Co-culture with E64d, an inhibitor of cysteine protease such as calpain, especially prevented nuclear opacities and proteolysis of crystallins, indicating that calpain was involved in cataract formation by diamide.
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PMID:Involvement of calpain in diamide-induced cataract in cultured lenses. 164 87

Extracellular fluid calcium is a tightly controlled variable. Hypoparathyroid state may result in profound calcium imbalance and moderate to severe hypocalcaemia. During 1974-89, 108 cases of hypoparathyroidism (97 post-surgical and 11 idiopathic) were seen. In the post-thyroidectomy group, 83 cases (85%) presented with acute transient hypocalcaemia with spontaneous recovery within 7-10 days. Chronic hypoparathyroidism was seen in 25 cases (14 post-surgical and 11 idiopathic). Convulsions resembling epileptic fits were seen in 9 cases (36%). Pseudopapilloedema was seen in three cases presenting with fits. The administration of phenobarbitone and dilantin aggravated convulsions in 9 patients. The other manifestations were psychiatric illness, cataract and calcification of basal ganglion. Biochemical findings included persistent hypocalcaemia with normal or raised serum phosphorus and lowered daily urinary excretion of calcium. Twenty three of 25 chronic hypoparathyroid cases were treated with vitamin D3 (1-3 mg/day) and calcium supplements (600-1000 mg/day)while 1 alfa-calcidol or calcitriol was used in two patients. Four patients receiving treatment with vitamin D3 developed transient hypercalcaemia with raised plasma levels of 25 hydroxy-vitamin D3. They responded to a reduction in dosage of vitamin D3. One patient was later changed over to 1-alfa-calcidol and another to calcitriol.
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PMID:Calcium imbalance in hypoparathyroidism. 130 51

A previous observation of increased aqueous magnesium in eyes with senile cataract has been re-examined in a totally different material. The serum and aqueous level of calcium and magnesium from 34 patients with senile cataract were tested against comparable values from 4 patients with choroidal melanoma. In contrast to calcium, the magnesium aqueous/serum ratio was significantly higher in the cataract group. Possible explanations are suggested.
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PMID:Increased magnesium in aqueous humour from patients with senile cataract. 175 Mar 27

Selenite (Se) cataract in rabbit lenses was investigated in vitro to define target sites of Se that might be involved in calcium elevation and lens opacification. Experiments in which the anterior or the posterior surface of the lens was exposed to Se showed that anterior exposure led to ionic imbalances and opacification in the whole lens. Posterior exposure to Se (1 mM, 2 hr) had no effect. Se treatment (0.1 mM) of epithelial homogenates led to a 56% loss of thiol (SH) groups, and treatment of lenses cultured in Se led to a 22% loss. Experiments to assess the effects of Se on SH groups of Ca-ATPase showed that the transport enzyme was not affected by the poison. To determine whether this negative finding was due to the lack of accessibility of Se for SH sites in an ordered membrane, Ca-ATPase was also assayed in homogenate preparations treated with Se; still no inhibition of Ca-ATPase activity was observed. Therefore, an alternative explanation of calcium elevation was explored. The passive movement of labeled chloride (36Cl) was found to be twice as fast in Se-treated lenses as it was in control lenses. Measurement of the lens voltage indicated an 18-mV depolarization in Se-treated lenses, suggesting that Se increased membrane permeability. All cataractogenic changes that occurred after Se treatment were irreversible-despite intervention with external application of reduced glutathione or cysteine. This finding suggests that irreversible loss of SH groups in lens membranes is important in maintaining ion homeostasis.
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PMID:Effect of selenite on epithelium of cultured rabbit lens. 182 4

Cataracts were produced in cultured rat lenses by either 10 microM calcium ionophore A23187, 25 microM sodium selenite, or 30 mM xylose. E64, an inhibitor of cysteine proteases, such as calpain (EC, 3.4.22.17), reduced severity of cataract and proteolysis of crystallins when included at a 500 microM concentration in the culture medium along with cataractogenic agents. Calpain II enzyme activity and the amount of calpain antigen were decreased in the cytosol of cataractous lens. However, E64 caused an increase in the amount of an 80-kD calpain subunit associated with the ethyleneglycol-bis-(beta-aminoethylether) tetraacetic acid/ethylenediaminetetraacetic acid-washed insoluble proteins when lenses were incubated with cataractous agents. These data indicate that E64 was at least partially effective in inhibiting lens calpain, and that activation of lens calpain may involve binding to the insoluble fraction. These results provide strong evidence for the activation of calpain in rodent cataracts and suggest testing inhibitors of calpain as anticataract drugs.
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PMID:Amelioration of cataracts and proteolysis in cultured lenses by cysteine protease inhibitor E64. 184 10

To determine the biocompatibility of the expansile hydrogel intraocular lens, a two-year animal study was undertaken. After phacoemulsification, hydrogel expansile intraocular lenses were implanted in four Dutch-belted rabbit eyes. Slitlamp examinations revealed minimal anterior chamber reaction and lens synechias. Gross pathology and histology demonstrated hyperplastic residual cortex, but confirmed our clinical impression that the lenses were well tolerated. Electron diffraction energy dispersive X-ray microanalysis revealed deposition of aluminum, silicon, magnesium, and calcium, but there was no evidence of matrix penetration.
J Cataract Refract Surg 1991 Jul
PMID:Animal model experimentation using the expansile hydrogel intraocular lens. 189 27

The purpose of this experiment was to test the effectiveness of E64 in prevention of selenite nuclear cataract in the whole animal. E64 is an inhibitor of cysteine proteases such as calpain (EC.3.4.22.17). In the whole animal, daily intraperitoneal injection of E64 was mildly effective in slowing the rate of formation of selenite nuclear cataract, although prevention was not permanent. Frequency of the nuclear cataract in selenite group at 5 days post selenite injection was significantly decreased from 40% to 17% in the selenite + E64 group, and the density of cataract in the Se + E64 group was reduced. However, crystallins and calpain were still degraded in the selenite + E64 group. E64 was more effective against selenite cataract when present continuously during lens culture, where it slowed the rate of formation of nuclear opacity. Amelioration of cataract occurred both in vitro and in vivo even though lens calcium concentrations were elevated. The results supported the idea that application of calpain inhibitor is beneficial in prevention of rodent selenite cataracts.
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PMID:Cysteine protease inhibitor E64 reduces the rate of formation of selenite cataract in the whole animal. 191 2


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