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PubMed2001

Evidence for distinct cholesterol domains in fiber cell membranes from cataractous human lenses.

Previous studies in our laboratory have provided direct evidence for the existence of distinct cholesterol domains within the plasma membranes of human ocular lens fiber cells. The fiber cell plasma membrane is unique in that it contains unusually high concentrations of cholesterol, with cholesterol to phospholipid (C/P) mole ratios ranging from 1 to 4. Since membrane cholesterol content is disturbed in the development of cataracts, it was hypothesized that perturbation of cholesterol domain structure occurs in cataracts. In this study, fiber cell plasma membranes were isolated from both normal (control) and cataractous lenses and assayed for cholesterol and phospholipid. Control and cataractous whole lens membranes had C/P mole ratios of 3.1 and 1.7, respectively. Small angle x-ray diffraction approaches were used to directly examine the structural organization of the cataractous lens plasma membrane versus control. Both normal and cataractous oriented membranes yielded meridional diffraction peaks corresponding to a unit cell periodicity of 34.0 A, consistent with the presence of immiscible cholesterol domains. However, comparison of diffraction patterns indicated that cataractous lens membranes contained more pronounced and better defined cholesterol domains than controls, over a broad range of temperature (5-40 degrees C) and relative humidity (52-92%) levels. In addition, diffraction analyses of the sterol-poor regions of cataractous membranes indicated increased membrane rigidity as compared with control membranes. Modification of the membrane lipid environment, such as by oxidative insult, is believed to be one potential mechanism for the formation of highly resolved cholesterol domains despite significantly reduced cholesterol content. The results of this x-ray diffraction study provide evidence for fundamental changes in the lens fiber cell plasma membrane structure in cataracts, including the presence of more prominent and highly ordered, immiscible cholesterol domains.

Aged↗

PubMed1999

Prevalence and incidence of age-related cataract in a population sample from Priverno, Italy.

PURPOSE: To study the prevalence and incidence of age-related cataract in a random population sample from the town of Priverno in the Lazio Region, Italy. METHODS: In 1987, 860 people between the ages of 45 and 69 years, already participating in a study on cardiovascular risk factors, underwent an ophthalmological examination. Patients with lens opacities, assessed by a clinical biomicroscopy and a best-corrected VA equal to or worse than 0.2 LogMar (20/30), were defined as age-related cataract cases. Of the 828 patients without age-related cataract at the baseline, 602 were re-examined in 1994. The 7-year Cumulative Incidence was calculated in three ways, as follows: - referring to the baseline sample without age-related cataract; - referring to the follow-up sample without age-related cataract at baseline; and - adjusted for non-response to the follow-up. RESULTS: In the baseline sample, the prevalence of age-related cataract was 3.7% (2.7%-5.2%, 95% C.I.). Cumulative Incidence referring to the baseline sample was 6.5% (4. 8%-8.2%, 95% C.I.); Cumulative Incidence referring to the follow-up sample was 9.0% (6.7%-11.3%, 95% C.I.). Adjusted Cumulative Incidence of age-related cataract was 7.6% (5.6%-9.5%, 95% C.I.). CONCLUSIONS: The study suggests that, in the Priverno sample, aging, but not gender, is a very important risk factor for cataract. The authors conclude that more information is needed on incidence of age-related cataract needing surgical rehabilitation and on risk factors causing both progression of lens opacities and visual loss.

Age Distribution↗

PubMed1999

Incident cataract after a five-year interval and lifestyle factors: the Beaver Dam eye study.

CONTEXT: A population-based study to investigate risk factors for age-related eye disease was begun in 1987 in a representative American community. Incidence of cataract was subsequently evaluated. SPECIFIC OBJECTIVES: To examine the relationships of cigarette smoking, alcohol, and caffeine intakes to incidence of age-related cataracts five years later. DESIGN: Observational epidemiologic incidence study of an adult population. PARTICIPANTS AND INTERVENTION: Adults 43-84 years of age were identified during a census in 1987-1988, and examined at baseline (1988-1990) and after a five-year interval (1993-1995). MAIN OUTCOME MEASURE: Standardized protocols were used at the baseline and follow-up evaluations for exposures and for objective identification of cataracts. RESULTS: Cumulative incidence of nuclear cataract in right eyes was about 12%, cortical cataract about 8%, and posterior subcapsular cataract about 3%. In multivariable analyses of the general estimating equations type, there were significant associations between nuclear cataract and: pack-years smoked (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01, 1.09 per 10 pack-years); and current alcohol intake (OR 1.01, 95% CI 1.00, 1.02 per 10 grams ethanol/week). Cigarette smokers were more likely to have had cataract surgery in the interval between baseline and follow-up examinations. CONCLUSIONS: Cigarette smoking and alcohol consumption were associated with modestly increased risks of incident nuclear cataract over a five-year interval.

Adult↗

PubMed2005

Posterior polar cataract: genetic analysis of a large family.

Congenital cataracts are clinically and genetically heterogeneous. Loci for autosomal dominant posterior polar cataracts have been mapped to chromosomes 1p36, 11q22-q22.3, 16q22, and 20p12-q12. We investigated a large four-generation family with 20 individuals affected with congenital posterior polar cataracts. After exclusion of known loci for posterior polar cataracts, a genome-wide screen was conducted. In this family, we mapped dominant congenital posterior polar cataracts to chromosome 10q24. On haplotype analysis, we identified an 11-cM interval between loci D10S1680 and D10S467, which included the PITX3 gene. On sequencing the coding region of PITX3, we found a 17-base-pair duplication in exon 4. Although the same genotype was described in a family with ASMD and cataracts, the common phenotype of this mutation is probably posterior polar cataract; a modifier gene is presumed to cause anterior segment abnormalities in the previously described patients. The same mutation was recently identified in four families with congenital cataracts. This study provides further evidence of genetic heterogeneity of autosomal dominant posterior polar cataract.

Amino Acid Sequence↗

PubMed1999

Serum carotenoids and tocopherols and incidence of age-related nuclear cataract.

BACKGROUND: It is not known whether the protective effects of antioxidants on cataract observed in experimental animals are relevant to age-related opacities in humans. OBJECTIVE: The relations of serum carotenoids and tocopherols to the incidence of age-related nuclear cataract were investigated in a random sample of 400 adults, 50-86 y of age, in the Beaver Dam Eye Study. DESIGN: Nuclear opacity was assessed by using lens photographs taken at baseline (in 1988-1990) and follow-up (in 1993-1995). Nonfasting concentrations of individual carotenoids and alpha- and gamma-tocopherol, were determined from serum obtained at baseline. A total of 252 persons were eligible for incident cataract, of whom 57 developed nuclear cataract in at least one eye. Results were adjusted for age, smoking, serum cholesterol, heavy drinking, adiposity, and, in the tocopherol models, dietary linoleic acid intake. RESULTS: Only serum tocopherol (the sum of alpha- and gamma-tocopherol, in micromol/mmol cholesterol) was associated with cataract. For total serum tocopherol, persons in tertile 3 had a lower risk of cataract than persons in tertile 1 [odds ratio (OR): 0.4; 95% CI: 0.2, 0.9; P = 0.03 for linear trend]. Although serum carotenoids were not significantly associated with nuclear cataract, marginal inverse associations with lutein (OR: 0.3; 95% CI: 0.1, 1.2; P = 0.13 for linear trend) and cryptoxanthin (OR: 0.3; 95% CI: 0.1, 1.3; P = 0.11 for linear trend) were suggested in people < or = 65 y of age. CONCLUSIONS: Findings were compatible with the possibility that nuclear cataract may be linked inversely to vitamin E status, but neither strongly supported nor negated the hypothesized inverse association of nuclear cataract with serum carotenoids.

Age Factors↗

PubMed2004

Dietary glycemic load and risk of age-related cataract.

BACKGROUND: Metabolism of many of the most commonly consumed carbohydrates in the United States results in a high plasma glucose response, which can be quantified by the glycemic load. Although hyperglycemia is a risk factor for cataract, there is no information on the potential effect of a high dietary glycemic load on the incidence of age-related cataract. OBJECTIVE: Our objective was to prospectively examine the association between dietary glycemic load and incident age-related cataract. DESIGN: We studied 2 cohorts-71 919 women and 39 926 men-aged > or =45 y who had no previous diagnosis of cataract, diabetes mellitus, or cancer and who were followed for 14 and 12 y, respectively, for the occurrence of cataract extraction. We calculated dietary glycemic load from data reported on multiple validated food-frequency questionnaires and used pooled logistic regression models to estimate the association with incident cataract extraction. We performed analyses separately for each cohort and then calculated pooled estimates across cohorts. RESULTS: During 980 683 person-years of follow-up, we confirmed 4865 incident age-related cataract extractions. After adjustment for age, cigarette smoking, body mass index, total caloric intake, dietary intake of lutein and zeaxanthin, and alcohol consumption, there was no significant relation of dietary glycemic load to risk of cataract extraction (P for trend = 0.10). The pooled relative risk between the highest and lowest quintiles of dietary glycemic load was 0.95 (95% CI: 0.81, 1.11; P for heterogeneity by cohort = 0.1). CONCLUSION: These prospective epidemiologic data do not support the hypothesis that a high dietary glycemic load, primarily a result of consumption of refined carbohydrates, increases the risk of cataract extraction.

Cataract↗

PubMed2004

Characterization of the G91del CRYBA1/3-crystallin protein: a cause of human inherited cataract.

Congenital cataract is a leading cause of visual disability in children. Inherited isolated (non-syndromic) cataract represents a significant proportion of cases and the identification of genes responsible for inherited cataract will lead to a better understanding of the mechanism of cataract formation at the molecular level both in congenital and age-related cataract. Crystallins are abundantly expressed in the developing human lens and represent excellent candidate genes for inherited cataract. A genome-wide search of a five-generation family with autosomal dominant lamellar cataract demonstrated linkage to the 17p12-q11 region. Screening of the CRYBA1/3 gene showed a 3 bp deletion, which resulted in a G91del mutation within the tyrosine corner, that co-segregated with disease and was not found in 96 normal controls. In order to understand the molecular basis of cataract formation, the mutant protein was expressed in vitro and its unfolding and refolding characteristics assessed using far-UV circular dichroism spectroscopy. Defective folding and a reduction in solubility were found. As the wild-type protein did not refold into the native conformation following unfolding, a corresponding CRYBB2 mutant was genetically engineered and its refolding characteristics analysed and compared with wild-type CRYBB2. Its biophysical properties support the hypothesis that removal of the glycine residue from the tyrosine corner impairs the folding and solubility of beta-crystallin proteins. This study represents the first comprehensive description of the biophysical consequences of a mutant beta-crystallin protein that is associated with human inherited cataract.

Amino Acid Sequence↗

PubMed2006

Effect of cataract on frequency doubling perimetry in the screening mode.

PURPOSE: To determine the effect of cataract on frequency doubling perimetry in the screening mode. METHODS: Frequency doubling technology perimetry in the C-20-5 screening mode was performed prospectively on 34 patients with otherwise healthy eyes before and after phacoemulsification. Cataracts were scored using the LOCS III classification, and the number of missed points (at any level of severity) on the screening field was compared before and after surgery. RESULTS: Nine patients missed at least one point pre-operatively and had no misses post-operatively. Those patients with posterior subcapsular (PSC) cataract were significantly more likely to miss points on the screening frequency doubling technology perimetry than those without posterior subcapsular cataracts (P < 0.001; Fisher exact test). In addition, the degree of posterior subcapsular cataract strongly correlated with the number of missed points pre-operatively (r = 0.97). The degree of nuclear sclerotic cataract did not correlate strongly with the number of missed points (r = 0.26), but the correlation was slightly stronger in the presence of cortical cataract (r = 0.36). CONCLUSION: Advanced age-related cataracts may cause false positive results on the screening frequency doubling technology, and the presence of even mild posterior subcapsular cataract may be a cause of false positive results and should be taken into consideration when interpreting the screening frequency doubling technology perimetry results.

Aged↗

PubMed1997

Lack of association between localized cataract and visual field loss: the Blue Mountains Eye Study.

PURPOSE: To examine whether localized cataract is related to localized field defects on suprathreshold visual field testing. METHODS: Suprathreshold screening visual fields (Humphrey 76-point test) and lens photographs, graded using the Wisconsin System, were performed on participants attending the Blue Mountains Eye Study, which examined 3654 subjects residing in an area west of Sydney, NSW, Australia. The results for 2276 subjects were analysed in the present study. RESULTS: There were no significant relationships between total points missing in the visual field and the degree of cortical, posterior subcapsular (PSC) or nuclear cataract after adjusting for confounders (test for trend P = 0.9, 0.7 and 0.9, respectively). Adjusted prevalence ratios and 95% confidence limits for the association between 10 or more points missing and the presence of cataract were 0.94 (0.77-1.25) for cortical, 1.26 (0.82-1.93) for PSC and 1.06 (0.86-1.30) for nuclear cataract. Similarly, there was no relationship between the presence of cortical or PSC cataract and sectoral visual field loss in any quadrant or hemifield. CONCLUSIONS: Neither cortical, nuclear nor PSC cataracts increase the total points missing on the 76-point suprathreshold field test. Similarly, neither cortical nor PSC cataracts cause sectoral visual field loss on this screening field test. In the presence of cataract, sectoral visual field loss on non-thresholding visual field screeners must be attributed to other causes, such as glaucoma. The present study provides a clinical alert that localized field loss is unlikely to be related to cataract.

Aged↗

PubMedDate not supplied

Inheritance of cataract in the Bichon Frise.

OBJECTIVE: To determine the mode of inheritance of cataract formation in the Bichon Frise. MATERIALS: Thirty-six closely related Bichon Frise dogs in a pedigree of 61 dogs were examined using slit-lamp biomicroscopy and indirect ophthalmoscopy over a period of 10 years. RESULTS: Of the 61 related dogs, 36 were examined repeatedly. Twelve cataractous dogs were diagnosed (three males and nine females). Cataractous dogs resulted from matings between unaffected parents, and when one parent was cataractous and the other parent was unaffected. Age at onset of cataract formation ranged from 18 to 160 months. Available information suggests that the cataracts are inherited as an autosomal recessive trait. CONCLUSION: Cataracts appear inherited in the Bichon Frise as an autosomal recessive trait. Additional cataract x cataract matings are necessary to confirm the autosomal recessive heredity.

Animals↗

PubMedDate not supplied

Cataract in the UK Leonberger population.

OBJECTIVE: To survey the Leonberger, a numerically small breed in the UK, for the presence of cataract and find statistical support for the possible presence of inherited forms of cataract. METHODS: Ocular examinations were carried out by the first author between September 1996 and September 1998 on 211 Leonbergers; results of the ocular examination of further 228 Leonbergers examined between January 1990 and September 1998 by members of the British Veterinary Association/KC/ISDS eye scheme (BVA/KC/ISDS eye scheme) panel were analyzed. Data from all dogs examined were pooled in a composite database of 365 Leonbergers and the relationships between offspring and parents for the identified forms of cataract were examined with appropriate statistical methods. RESULTS: Cataracts were diagnosed in 90 Leonbergers, the majority being nuclear (40) or posterior polar subcapsular (31). A subgroup of nuclear cataracts, diagnosed in 11 dogs, is described and named as 'posterior nuclear cataract.' For posterior polar cataract, a positive association between offspring and parents was made in the logistic regression model, supporting the suggestion of inheritance. CONCLUSIONS: The presence of several types of cataract in the UK Leonberger population is described. Statistical support for the inheritance of posterior polar subcapsular cataract is given.

Animals↗

PubMed2005

The impact of cataract severity on measurement acquisition with the IOLMaster.

PURPOSE: The Zeiss IOLMaster optical biometry system provides superior prediction of refractive outcome of cataract surgery compared to applanation ultrasound. However, measurement is not always possible in the presence of dense cataract. The purpose of this study was to elucidate the rate of measurement acquisition failure due to cataract and how this varies with morphology and severity. METHODS: A total of 149 subjects were prospectively enrolled and visual acuity, Lens Opacities Classification System III (LOCS III) scores, ultrasonic A-scan and IOLMaster axial lengths were measured. Chi-squared analysis was used to test the null hypothesis that cataract severity has no effect on measurement failure rate. RESULTS: Measurements could not be obtained with the IOLMaster in nine cases for reasons other than cataract. Cataract caused measurement acquisition failure in 22 (15.9%) cases, including all mature cataracts (n=3) and posterior subcapsular cataracts (PSC) with LOCS III (p>3.5; n=18). The null hypothesis was accepted for cortical (chi(2)=2.94, d.f.=2, p>0.05) and nuclear (chi(2)=7.91, d.f.=4, p>0.05) ataract, but rejected for PSC (chi(2)=111, d.f.=3, p<0.001). All cases could be measured with ultrasound. CONCLUSIONS: The IOLMaster fails to acquire axial length measurement in approximately 20% of UK public hospital cataract patients. Failure is principally due to PSC, whereby the LOCS III score of p=3.5 defines the limit of PSC severity that the IOLMaster can measure.

Adult↗

PubMed1989

Associations between nutrition and cataract.

Blindness due to opacification of the lens, or cataract, afflicts 50 million persons worldwide. In the United States over 541,000 cataract extractions are done annually at a cost of over $3.8 billion. Conservative estimates indicate that the prevalences of cataracts in Americans aged 65-75 and 75-85 years are 18% and 46%, respectively. Cataracts are even more prevalent in some other populations. It is estimated that the need for cataract extractions would be diminished by half if onset of cataract could be delayed by only ten years. Hypotheses regarding the etiology of cataract include oxidative perturbations of protein metabolism, diverse pathologic conditions, and perhaps glycation of lens proteins. Epidemiologic data indicate that elevated plasma levels of specific nutrients (i.e., carotenoids, ascorbate, tocopherol, and taurine) are associated with diminished incidence of certain types of cataract. Biochemical evidence suggests that each of these compounds can delay photooxidative damage to lens proteins. Roles in lens metabolism for selenium and tryptophan have been suggested. Elucidation of mechanisms by which caloric restriction delays cataract development is a promising area of current research.

Cataract↗

PubMed1992

Light scatter in aging and cataractous human lens.

We measured back light scattering of the human lens with the Lens Opacity Meter 701 in order to determine whether it can be used for objective assessment of lens opacities in various types of cataracts. One-hundred and twenty-seven eyes of 127 individuals were examined including 43 healthy volunteers in various age groups and 84 patients with cortical, nuclear, posterior subcapsular or mixed lens opacities. Almost 90% of the total variation in the light scatter values was accounted for by age in non-cataractous eyes. Mean scatter value of every cataract group was statistically significantly higher than that of age matched healthy controls (p less than 0.0001). Highest scatter values were measured in cortical cataracts while the mean values of other types of cataract were not statistically significantly different from each other. The regression between light scatter and visual acuity was statistically significant for each cataract group. However, large variation of visual acuity was found with scatter values below 60. The results indicate that the Interzeag Lens Opacity Meter is able to identify cataractous and non-cataractous eyes and discern at least advanced cortical cataracts from other types of lens opacities.

Adolescent↗

PubMed1994

Dose-response characteristics of galactose-induced cataract in the rat.

The onset and progression of cataract was investigated in weanling Sprague-Dawley rats fed 10, 15, 20 and 30% dietary galactose (groups 1-4) for 45-226 days. Cataracts were graded on a 0-5 scale. After 226 days, 9% of the rats fed 10% galactose developed lesions beyond the very early stage of cataractogenesis (grade 1). After 154 days 50% of the rats fed 15% galactose developed subcortical cataract (grade 3) with no nuclear cataract. In the rats fed 20% galactose, an initial rapid development by 31 days of a grade 3 cataract was observed in 50% of the eyes. Advancement to grade 4 and grade 5 cataract proceeded more slowly; by 207 days, 45% of the eyes had grade 5 cataract. In rats fed 30% galactose, rapid vacuolization and development of nuclear cataracts (grade 5) were observed by day 44. Dietary galactose at levels of 20 and 30% was associated with a significant reduction in weight gain at the early stage of dietary treatment. These observations demonstrate that 10-30% dietary galactose induces cataract in rat lens in a dose- and time-dependent fashion. These data serve to further establish this animal model as a useful model for studying the sequelae of cataractogenesis.

Animals↗

PubMed1995

Ten years of cataract epidemiology studies in the Department of Experimental Ophthalmology, 1980-1990.

The knowledge of the multifactorial genesis of the so-called senile cataract has initiated an intensified search for cataract-related risk factors. The mechanisms of syn- and cocataractogenesis could already be shown in the Department of Experimental Ophthalmology, Bonn, in the seventies. Subsequently, cataract epidemiology became a field of interest in 1980 when all available epidemiological data related to cataract research were first collected and reviewed. It has become obvious that the various types of cataract morphology do not represent one unique disease 'senile cataract' but reflect different biochemical characteristics. A preliminary study assigned data of case history as well as blood and lens biochemistry to four types of lens opacity. Scheimpflug photography and multilinear microdensitometry were the basis for classifying cataract lenses. After increasing the number of involved patients, the data were analyzed by means of multivariate statistics. The originally used cataract classification system was enlarged to eight types of frequently seen cataract morphologies. A control group was built up to enable case-control studies as well as to obtain characteristics of normal lens density related to age.

Aged↗

PubMed2004

Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE: To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. METHODS: All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. RESULTS: Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. CONCLUSIONS: Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.

Aged↗

PubMed2004

Lenticular levels of amino acids and free UV filters differ significantly between normals and cataract patients.

PURPOSE: To determine the levels of free UV filters and selected amino acids in cataract lenses compared with normal lenses. METHODS: Indian cataract lenses (n=39) and normal lenses (n=6) were examined by HPLC to quantify levels of UV filter compounds, the UV filter precursor amino acid tryptophan (Trp), as well as tyrosine (Tyr) and uric acid. RESULTS: The levels of the two major primate UV filters, 3-hydroxykynurenine glucoside (3OHKG) and 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside (AHBG), in cataract lenses were markedly decreased compared with levels in normal lenses. By contrast, the levels of Trp were greatly increased. Mean Trp concentrations were an order of magnitude higher than in normal lenses, with 86% of dark-colored cataract lens nuclei having Trp concentrations greater than the mean level in the normal lenses. The concentrations of Tyr were also higher in cataract lenses. The levels of Kyn, however, were unchanged, and the uric acid levels were substantially lower. CONCLUSIONS: The levels of the free UV filter compounds 3OHKG and AHBG, and also of Trp, Tyr, and uric acid were different in cataract lenses compared to normal lenses. These data suggest that the metabolism of a large proportion of patients with cataract may be substantially different than in persons with normal lenses. Although the mechanism of such metabolic defects are unknown, the authors speculate that an amino acid transporter system may be upregulated in patients with cataract. Because kynurenine levels in cataract were not significantly different from those of normal lenses, there may be a defect in the lenticular UV filter pathway at one, or both, of the steps that convert kynurenine to 3OHKG.

Adult↗