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PubMed2003

Existence of deamidated alphaB-crystallin fragments in normal and cataractous human lenses.

PURPOSE: The aims of this study were to characterize lens crystallin fragments having a molecular mass of <10 kDa, isolated by solubilization in trichloroacetic acid, in order to identify cleavage sites in the parent crystallins for their origin and determine post-translational modifications in the fragments. METHODS: The water-soluble (WS) and water-insoluble (WI) protein fractions were isolated from normal human lenses of 60 to 80 year old donors and from age-matched cataractous lenses. Both WS and WI protein fractions were treated with TCA at 60 degrees C for 2 h and the TCA-soluble fractions were recovered following centrifugation. The preparations were dialyzed against H2O to remove TCA, concentrated by lyophilization and subjected to two dimensional gel electrophoresis (2D-GE). The spots from 2D-gels were analyzed by western blot analysis, partial N-terminal sequencing, or excised for mass spectrometric analysis. RESULTS: SDS-PAGE analysis showed that TCA solubilized polypeptides having a molecular mass of <10 kDa from both WS and WI protein fractions of normal and cataractous lenses. Following 2D-GE of TCA-solubilized species from normal lenses, 8 and 5 polypeptides from the WS and WI protein fractions, respectively, were observed. Using similar 2D-GE analysis of TCA solubilized species from cataractous lenses, 9 and 5 polypeptides from WS and WI protein fractions, respectively, were seen. Partial N-terminal sequence analysis showed that the majority of the polypeptides from both WS and WI protein fractions of normal and cataractous lenses were derived from alphaB-crystallin following cleavage at the D129-P130 bond. Western blot and partial N-terminal sequence analyses identified three additional 4-kDa alphaA-crystallin fragments with cleavage at the D136-G137 bond in the WS proteins from normal lenses. MALDI-TOF mass spectrometric analysis showed that all TCA soluble polypeptides from cataractous lenses, except one from normal lenses, contained residue number 130 to 175 from alphaB-crystallin. No further truncation occurred at the C-terminal region of the alphaB-crystallin polypeptides. Following comparison of the isotopic distribution in MALDI-TOF profiles of a tryptic fragment having a mass of 2,014 among the alphaB-crystallin polypeptides, a gain of one single Dalton was observed. This suggested deamidation of the N146 residue in alphaB-crystallin fragments. CONCLUSIONS: The results show that the N146 residue in human alphaB-crystallin undergoes in vivo deamidation and several fragments containing this modification exist in both WS and WI protein fractions of normal and cataractous human lenses.

Aged↗
PubMed2003

Selenite cataract and its attenuation by vitamin E in Wistar rats.

PURPOSE: To study the role of vitamin E in preventing cataract formation in experimental animals. METHODS: An experimental model (selenite cataract) was selected for this study. Selenite cataract was produced in rats by subcutaneous administration of sodium selenite. Biochemical and histological changes following induction of selenite cataract in weanling Wistar rats were studied vis-a-vis the role of vitamin E in attenuating or preventing cataractogenesis. RESULTS: Vitamin E was capable of preventing selenite cataractogenesis. Selenite cataract did not develop in 91.6% (11 of 12) and 76.7% (8 of 12) vitamin E treated rats, when administered on the 12th and 10th post partum day respectively. CONCLUSION: The study confirmed that selenite induced cataract in Wistar rats is attenuated by vitamin E.

Animals↗
PubMed1992

Cataract in renal transplantation recipients with combination ciclosporin treatment.

Post surgical cataracts induced by corticosteroids as immunosuppressive agents were investigated in recipients undergoing triple therapy with ciclosporin and the results were compared with those who had therapy without ciclosporin administration. The subjects of the triple therapy group were 54 cases with a mean age of 31.7 years. The mean observation period was 25 months. The incidence of posterior subcapsular cataract was 77.8%. 7.9% of them developed progressed cataract. Early cataractous changes were noticed within one post-operative year in half of the cases. 3 out of 22 cases that were followed up over three years showed progressed cataractous changes. The total doses of methylprednisolone during the period of the first post-transplant year in recipients with Grades I or II and over Grade III were 7.7 +/- 1.9g and 9.8 +/- 3.6g, respectively. They were significantly higher than those in the conventional therapy group. However, a 2 to 3 g reduction in the total dose of steroids during the first year had no influence on cataract occurrence.

Adolescent↗
PubMed1992

An application of ultrasonic tissue characterization to the diagnosis of cataract.

From a therapeutic and pathological point of view, it is important to classify types of cataract and to identify their stages. However, accepted criteria for quantitative diagnosis have not been established. On the other hand, based on the experience from tissue characterization applied to other clinical fields, the attenuation characteristics of the lens are expected to change according to the stage of disease and the type of cataract. In this study from echo signals we tried to measure the attenuation coefficient of the lens with the purpose of quantitatively diagnosing the cataract, and at an early stage. It is shown that the attenuation of the cataractous lens is larger than that of the normal lens and its value depends on the type of the cataract, an indication of the possibility of using tissue characterization in the evaluation of cataract.

Adult↗
PubMed1992

[Senile cataract and trachoma in Tunisia].

Senile cataract is the major cause of curable blindness in Tunisia (51%). Other factors than advanced age seem to play a role in senile cataract. The simultaneous of senile cataract with the trachoma makes the surgical operation problematic. In order to evaluate the frequency of such risk factors, we have realized a prospective study in two groups of patients recruited in 4 hospitals centers in Tunisia. The two groups of patients were homogenous regarding to age (more than 45 old year) sex and geographic origins. Cataract was present in the first group (287), but not in the second group (169) risk factors which were evidenced are: diabetes or abnormal glucose test tolerance, high systemic blood pressure, especially diastolic, low education and non professional occupation, family history of cataract. Evolutive trachoma was found in 5.1% of cases compared to only 0.6% in controls (p = 0.02). Trachoma sequela were found in the two groups. The importance of an evaluation of such risk factors in senile cataract is raised.

Aged↗
PubMed2003

[Surgery for treatment of senile cataract with Fuchs' endothelial dystrophy].

OBJECTIVE: To evaluate the result of surgery for senile cataract with Fuchs' endothelial dystrophy and emphasize the importance of the preoperative examination by specular microscopy. METHODS: In the review of 2,026 consecutive senile cataract cases, 17 Fuchs' endothelial dystrophy cases were found before cataract surgery by specular microscopy. Operative procedures and corneal endothelial protective measures were recorded, and postoperative corneal transparency was observed. The examination of specular microscopy was performed 3 months after the cataract surgery. RESULTS: The incidence of Fuchs' endothelial dystrophy in senile cataract was 0.8% (17/2,026) in our study. The loss rate of endothelial cells was 16.2%. No bullous keratopathy occurred in all cases during follow-up period. CONCLUSIONS: Reasonable measures to protect the endothelium in the surgery by an experienced operator is helpful to the success of surgery. Observing the endothelium by specular microscopy before cataract surgery is very important.

Aged↗
PubMed2004

Autosomal dominant coralliform cataract related to a missense mutation of the gammaD-crystallin gene.

BACKGROUND: Congenital cataract is a sight-threatening disease that affects about 1 - 6 cases per 10000 live births and causes 10% - 30% of all blindness in children. About 25% of all cases are due to genetic defects. We identified autosomal dominant congenital coralliform cataracts-related genetic defect in a four-generation Chinese family. METHODS: Complete ophthalmological examinations were performed prior to lens extraction. Lens samples were then studied by electron microscopy. Genomic DNA from family members were examined using whole-genomic linkage analysis, with two-point logarithm of odds (LOD) scores calculated using the Linkage program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing. Finally, a three-dimensional protein model was predicted using Swiss-Model (version 2.0). RESULTS: Eleven of the 23 examined individuals had congenital cataracts. Ultrastructure studies revealed crystal deposits in the lens, and granules extensively dispersed in transformed lens fiber cells. The maximum two-point LOD score, 3.5 at theta = 0.1, was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of gammaD-crystallin (CRYGD). Protein structure modeling demonstrated that the P23T mutation caused a subtle change on the surface of the gammaD protein. CONCLUSIONS: The results suggest that the coralliform cataract phenotype is due to a mutated CRYGD gene, and that this sequence change is identical to one reported by Santhiya to be related to another distinct clinical condition, lamellar cataract. This study provides evidence that this same genetic defect may be associated with a different phenotype. This is the first report identifying the genetic defect associated with an autosomal dominant congenital coralliform cataract.

Cataract↗
PubMed2004

[The influence of cataract surgery on the efficacy of trabeculectomy in patients with open-angle glaucoma].

PURPOSE: To study the influence of cataract surgery on the intraocular pressure decreasing effect of trabeculectomy in patients with open angle glaucoma. METHOD: Retrospective study that included two groups: --32 patients with open angle glaucoma, their intraocular pressure being controlled after filtering surgery; they were subject to cataract surgery at least 6 months after the trabeculectomy (the CT group)--44 patients with open angle glaucoma (primary or secondary) with intraocular pressure controlled after trabeculectomy (the T group). The evaluation included: preoperative intraocular pressure, early (at 2 months) and late (at 18 months) postoperative intraocular pressure, intra- and postoperative complications of the cataract surgery, the need for antiglaucoma medication. RESULTS: The cataract surgery in patients with trabeculectomy increases the intraocular pressure (initial mean IOP = 15.31 mmHg, final mean IOP = 18.53 mmHg, mean IOP = 3.22 mmHg). The intraocular pressure increase is more important after extracapsular extraction than after phacoemulsification (3.7 vs. 2.01 mmHg). Qualified therapeutical success was obtained in 81.25% of CT patients. In the T group the postoperative intraocular pressure maintained constant throughout the entire follow-up period. The number of additional antiglaucoma drugs was larger in the T group (0.7 versus 0.5). The patients that suffered intra and postoperative complications had increased intraocular pressure when compared to those without complications (mean IOP early = 3.1 mmHg, mean IOP late = 1.1 mmHg). CONCLUSIONS: Cataract surgery in patients with previous filtering surgery increases the intraocular pressure and the need for antiglaucoma drugs. The intraocular pressure rise was more important after extracapsular extraction than after phacoemulsification. Intra and postoperative complications result in a more important increase in intraocular pressure, in the first months after the cataract operation.

Aged↗
PubMed1992

Intraocular light scattering in age-related cataracts.

Intraocular light scattering was studied in 34 controls and 65 patients with cortical, nuclear, or posterior subcapsular cataracts by measuring forward scatter and backscatter. Forward scatter was measured by the psychophysical direct compensation method. Backscatter was determined with the Lens Opacity Meter of Interzeag. Contrast sensitivity loss caused by forward scatter was assessed with a glare tester (Vistech MCT 8000). Mean forward scatter was in the upper range for subcapsular cataracts compared to nuclear and cortical cataracts. Experimental results of the glare test (the contrast loss) deviated systematically from expected results based on measured forward scatter. Mean backscatter was largest for nuclear, intermediate for posterior subcapsular, and almost zero for cortical cataracts. Thus, each cataract has a characteristic mean ratio between forward scatter and backscatter. However, this ratio varied considerably among individuals, especially for cortical and posterior subcapsular cataracts. As a rule, forward scatter cannot be derived from backscatter (or the slit-lamp image).

Aged↗
PubMed1992

[Formation of congenital cataract in the offspring of galactosemic rats].

It has been established that lenses of offspring of galactosemic rats form sugar cataracts. In the present study, in order to clarify the critical period in pregnancy for the cataract formation, lenses of offspring of pregnant rats which were fed galactose diets at each of three terms of pregnancy, were examined histologically and biochemically. Severe cataract and a large amount of galactitol in the lenses were found in the offspring of rats fed a galactose diet in the last term of pregnancy. Moreover, focal cataract was found in the offspring of rats fed a galactose diet in the middle term. These results indicate that the critical period in pregnancy for cataract formation of the offspring is the last term of pregnancy and that cataract formation begins in the middle term in offspring of galactosemic rats.

Administration, Oral↗
PubMed2004

[Cataract surgery in Romania--2003].

AIM: to evaluate cataract surgery performed in Romania analyzing: --the number of cataract surgery performed in 2003; --the surgical technique used: intracapsular extraction, extracapsular extraction, phacoemulsification; --the number and type of intraocular lenses used; --the number of ophthalmologists that performed cataract surgery; MATERIAL AND METHOD: --a questionnaire was sent to all ophthalmologists which do cataract surgery. RESULTS: --38,000 surgeries for cataract were performed in 2003; --the surgical techniques used were : Phacoemulsification (18,000 cases), classic extracapsular extraction ( 19,000 cases) and intracapsular extraction (1000 cases); --28,500 rigid and 8,000 foldable intraocular lenses were implanted; - 223 ophthalmologists perform cataract surgery in Romania.

Cataract Extraction↗
PubMed2005

Doxorubicin-induced cataract formation in rats and the inhibitory effects of hazelnut, a natural antioxidant: a histopathological study.

BACKGROUND: To investigate whether hazelnut prevents doxorubicin-induced experimental cataract in rats. MATERIAL/METHODS: Seventy-five 4-week-old male Wistar albino rats were randomized into 5 equal groups. Beginning from 6 weeks of age, the groups were treated with intraperitoneal injections of saline solution or doxorubicin (DR) for 4 weeks. Group 1 received saline solution (0.5 ml/200 g) weekly, groups 2 and 4 a cumulative dose of 6 mg/kg (1.5 mg/kg/week) of DR, and groups 3 and 5 received a cumulative dose of 12 mg/kg (3 mg/kg/week) DR. All the rats were fed ad libitum with a 24% protein rodent chow. Groups 4 and 5 were additionally fed 5 g/day hazelnut. At the end of the tenth week the rats were sacrificed and cataract development was investigated histopathologically. The groups were statistically compared. RESULTS: All control lenses (group 1) were macroscopically clear. Cataractous changes were noted in 7 eyes (47%) in group 2 and in 10 (67%) in group 3 (p=0.01). Groups 3 and 5 had cataractous changes in 4 (27%) and 5 (33%) eyes, respectively (p=0.001). The cataract development ratio was different between groups 2 and 4 (p=0.013), while there was no such difference between groups 3 and 5 (p=0.053). Histopathological findings suggesting cataractogenesis were eosinophilic degeneration, cortical lens-fiber cell swelling, and the retention of nuclei in central fibers. CONCLUSIONS: Hazelnut prevented doxorubicin-induced cataract in low doses. Since it has no known harmful effect on healthy cells, it may be beneficial in humans.

Animals↗
PubMed2006

A missense mutation in the gammaD-crystallin gene CRYGD associated with autosomal dominant congenital cataract in a Chinese family.

PURPOSE: To identify the genetic defect in autosomal dominant congenital cataracts in a six generation Chinese family. METHODS: Clinical and ophthalmological examinations were performed on the affected and unaffected family members. All the members were genotyped with microsatellite markers at loci which were considered to be associated with cataracts. A two-point LOD score was calculated using the Linkage package after genotyping. A mutation was detected by direct sequencing using gene specific primers. RESULTS: Clinical heterogeneity was observed within this family, three affected individuals showed nuclear cataract and others had coralliform cataracts. Significant evidence of linkage was obtained at markers D2S325 (LOD score [Z]=3.10, recombination fraction [theta]=0.0) and D2S1782 (Z=5.97, theta=0.0), respectively. Haplotype analysis indicated that the cataract gene was close to those two markers. Sequencing of the gammaD-crystallin gene (CRYGD) revealed a C>T transition in exon 2, that causes a conservative substitution of Arg to Cys at codon 14 (R14C). This mutation co-segregated with all affected individuals and was not observed in unaffected or 100 normal unrelated individuals. Bioinformatic analyses also showed that a highly conserved region was located at Arg14. CONCLUSIONS: This study is the first reported case with phenotype of coralliform/nuclear cataract that associated with the mutation of Arg14Cys (R14C) CRYGD.

Adolescent↗
PubMed2006

Novel mutations in GJA8 associated with autosomal dominant congenital cataract and microcornea.

PURPOSE: The purpose of this study was to estimate the importance of mutations in the connexin50 gene (GJA8) as a cause of congenital or developmental cataracts in the Indian population and to identify novel mutations in GJA8 that cause cataract in this population. METHODS: The coding region of GJA8 was analyzed for mutation by single strand conformational polymorphism in 60 probands affected with congenital or developmental cataract of which 11 probands' corneal diameter measured less than 11.00 mm. Direct sequencing was performed for samples that displayed an abnormal electrophoresis pattern. The segregation of the change with the diseased phenotype was analyzed in the entire pedigree by restriction fragment length polymorphism (RFLP) analysis. RESULTS: Molecular analysis of GJA8 revealed two novel missense mutations V44E and R198Q, in the population screened. The mutations cosegregated with the diseased phenotype in an autosomal dominant manner and were absent in 400 normal control chromosomes analyzed. GJA8 mutations were seen in two of the 60 unrelated probands with cataracts. Affected individuals in both of whose families also had microcornea and variable myopia. CONCLUSIONS: This is the first report of mutations in GJA8 to be associated with autosomal dominant cataract and microcornea. Mutations in GJA8 cause 3.3% of congenital cataracts in the population of India.

Adult↗
PubMed2006

A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family.

PURPOSE: The molecular characterization of an Indian family having 10 members in four generations affected with a unique fan-shaped cataract-microcornea syndrome. METHODS: Detailed family history and clinical data were recorded. A genome-wide screening by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bi-directional sequencing of amplified products. RESULTS: The cataract-microcornea locus in this family was mapped to a 23.5 cM region on chromosome 21q22.3. Direct sequencing of the candidate gene CRYAA revealed a heterozygous C>T transition resulting in the substitution of the highly conserved arginine at position 116 by cysteine (R116C). CONCLUSIONS: This study provides the report of mapping a locus for syndromal cataract (cataract-microcornea syndrome) on 21q22.3. The mutation observed in CRYAA in the present family highlights the phenotypic heterogeneity of the disorder in relation to the genotype, as an identical mutation has previously been reported in an American family with a different type of cataract. The "fan-shaped cataract" observed in the present family has not been reported before.

Asian People↗
PubMed2006

The antagonism of cholecystokinin octapeptide-8 to the peroxynitrite oxidation on a diabetic cataractal rat model.

BACKGROUND: Cataracts is considered be formed because of an abnormal glucose metabolic pathway or oxidative stress. We explored the damaging role of ONOO- and antagonism of cholecystokinin octapeptide-8 (CCK-8) in diabetic cataractal rat lenses. METHODS: A diabetic cataractal animal model was established by peritoneal injection of streptozotocine (STZ). Thirty-six normal SD rats were taken as control group; seventy-two were given STZ (45 mg/kg) and then divided into STZ group and CCK-8 group (peritoneal injection CCK-8). STZ induced diabetic rats were treated with CCK-8 for 60 days. Lenses were examined with slit lamp at 20, 40 and 60 days. Immunofluorescent staining and Western blot analysis were used for determining nitrotyrosine (NT, a marker for ONOO-). PT-PCR and gene array analysis were used for determining the expression of inducible nitric oxide synthetase mRNA (iNOS mRNA) in lens epithelium (LEC). RESULTS: STZ group rats developed lens opacity by 20 days that reached a high level by 60 days after STZ injection. CCK-8 group rats delayed the cataract formation. CCK-8 group rats delayed the cataract formation. There was no distinct expression of NT and iNOS mRNA in control group. In STZ group, there were distinct expression of NT and upregulation of iNOS mRNA; however, CCK-8 group showed weak expression of NT and downregulation of iNOS mRNA. CONCLUSIONS: NT, which may be a new form of oxidative stress, was expressed in diabetic rat LEC although CCK-8 could reverse NT damage in LEC. The results suggested that CCK-8 might be a useful therapeutic agent against diabetic cataract. The antagonizing mechanism of CCK-8 may be related to direct antagonism of ONOO- as well as its inhibition of the expression of iNOS mRNA for production of NO and therefore decrease in the formation of ONOO-.

Animals↗
PubMed1991

[Localization of glutathione-S-transferase in transparent and cataractous human lenses].

The localization of glutathione-S-transferase (GST) activity was investigated in 15 cataractous lenses obtained by intracapsular extraction of senile cataract. Additionally, 8 clear lenses, obtained from donor eyes in cases of corneal transplantation or of traumatic lens luxation, were used as controls. The lenses were divided into the central and peripheral portions with a trephine. The activity of GST was quantitated in each portion according to the method described by Habig. GST activity in clear lenses was significantly higher in the peripheral portion than in the central portion and in the former it was significantly higher in clear lenses than in cataractous ones. The ratio of GST activity between central and peripheral portions (C/P) was significantly higher in cataractous lenses than in clear ones. These findings suggested that the scavenging system of the human clear lens is more active in the equatorial portion than in the central portion. Nevertheless the activity of GST in human cataractous lenses decreased more significantly in the peripheral portion than in the central portion. These findings indicated that the human cataract usually develop from equatorial portion of lens.

Adult↗
PubMed1991

Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat.

Naphthalene feeding can result in cataract formation in rats and rabbits due to specific metabolites of naphthalene. The concomitant administration of the aldose reductase inhibitor Al1576 to naphthalene-fed rats was proven to prevent cataract formation. To determine whether this effect was directly linked to the ability of Al1576 to inhibit enzyme aldose reductase, a variety of structurally diverse aldose reductase inhibitors, including the carboxylic acids tolrestat, Ponalrestat, and FK366, and the spirohydantoins, sorbinil and Al1576, were investigated for their ability to inhibit naphthalene-induced cataracts. Brown Norway rats, administered naphthalene by gavage, were fed normal rat chow containing these aldose reductase inhibitors at levels known to inhibit sugar cataract formation. The lens changes in these rats were monitored over a 90-day period by portable slit-lamp microscopy and histologic study. Al1576 showed a dose-dependent reduction in naphthalene-induced cataract formation, with no naphthalene-associated deposits seen in toluidine blue-stained lens sections. Sorbinil also reduced lens changes, whereas tolrestat, Ponalrestat, and FK366 had no effect. These results suggest that inhibition of naphthalene-induced cataract formation by structurally diverse aldose reductase inhibitors was not linked to the inhibition of aldose reductase.

Aldehyde Reductase↗