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Cysteine protease inhibitor E64 reduces the rate of formation of selenite cataract in the whole animal.

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.

Animals↗

Review of selenite cataract.

Recent advances in understanding the mechanism of selenite cataract have resulted from locating the cleavage sites on proteolyzed beta-crystallins from the cataract, mimicking the insolubilization of crystallins found in the cataract in an in vitro system, studying cataract produced in lenses cultured in selenite, and permanently or temporarily reducing the rate formation of selenite cataract by use of various inhibitors. The present review discusses the selenite cataract as a useful model for understanding the role calcium-induced proteolysis in cataract formation.

Amino Acid Sequence↗

Cataract incidence and analysis of lens crystallins in the water-, urea- and SDS-soluble fractions of Emory mice fed a diet restricted by 40% in calories.

Restriction of dietary calorie intake is associated with life extension and with the delay of age-related disorders. Preliminary studies demonstrated that by feeding the Emory mouse a diet restricted by 21% in calories cataract and insolubilization of protein could also be delayed. To observe the effects of calorie restriction over prolonged portions of adulthood, Emory mice were fed the control diet (C) or a diet restricted by 40% in calories (R). Feeding the R diet was associated with delayed formation or progress of cataract over virtually the entire second half of life. At 11 months of age, bilateral grade 5 cataracts were present in 17% and 2% of C and R lenses, respectively. At 22 months of age, bilateral grade 5 cataracts were present in 90% and 18% of C and R lenses, respectively. The distribution of alpha-, beta-, and gamma- crystallins in the water-soluble, urea-soluble, and SDS-soluble fractions indicates more similarities than differences between C and R lenses with a specific grade of cataract or of a given age. However, there were significant and abrupt (after grade 4 cataract) losses of particular gamma-crystallins; gamma-crystallins which were not prominent at earlier stages became the major gamma-crystallin moieties. Losses of alpha-crystallins were also noted upon cataract formation or aging in most of the fractions. Aggregates including gamma- and alpha-crystallins also accumulate faster in the C group.

Aging↗

EM immunolocalization of alpha-crystallins: association with the plasma membrane from normal and cataractous human lenses.

PURPOSE: To integrate past biochemical findings with past morphological observations of area insoluble material isolated from cataract and aged normal lenses, by determining the spatial distribution of alpha-crystallins associated with the plasma membrane (PM) of nuclear cataractous and age matched normal human lenses. METHODS: Lenses were homogenized, pelleted and washed several times in 0.05M Tris-Cl (pH 7.2) containing 100mM KCl, 1 mM MgCl2 and 2mM beta-mercaptoethanol, followed by several washes in 8M urea. Urea insoluble pellets (UIP) were labeled before fixation and embedding with rabbit serum raised against alpha-crystallins, followed by goat anti-rabbit IgG conjugated to 5nm gold. Approximately 300 gold particles associated with the PM were counted, for each lens, on several electron microscopy (EM) micrographs. The number of gold particles/um of PM, number of individual vs clusters of gold particles were determined. RESULTS: Micrographs from both normal and cataractous human lenses clearly demonstrated the association of alpha-crystallins with the PM. Also apparent was the abundant labeling of the PM for cataractous lenses as compared to normal lenses. Quantification of the gold labeling revealed that not only was there an increase in the amount of labeling/um of PM in cataract lenses, but there was also an increased percentage of gold in clusters. These clusters were not only more numerous in cataractous lenses, but also contained a greater number of gold/cluster. CONCLUSIONS: These findings provide morphological evidence that the PM in nuclear cataract lenses is associated with large aggregates of alpha-crystallin.

Aged↗

Cataract extraction in Behçet's disease.

AIMS/BACKGROUND: To assess the outcome and complications of cataract extraction in patients with Behçet's disease. METHODS: Thirty-six Behçet's disease patients underwent cataract surgery without intraocular lens implantation. Twenty-six patients had phacoemulsification or extracapsular cataract extraction, and ten patients had pars plana lensectomy/vitrectomy. The follow-up period ranged from 24 to 84 months (mean, 38 months). RESULTS: There was no statistically significant difference in the follow-up period of patients who underwent phacoemulsification, extracapsular cataract extraction, or pars plana lensectomy/vitrectomy. Sixteen (62%) of 26 patients who had extracapsular cataract extraction or phacoemulsification had a visual acuity of 20/200 or better compared with none of the 10 patients who had pars plana lensectomy/vitrectomy. Three (30%) of ten eyes which underwent pars plana lensectomy/vitrectomy eventuated in phthisis bulbi while none of the eyes that underwent extracapsular cataract extraction or phacoemulsification developed phthisis bulbi. CONCLUSION: Extracapsular cataract extraction or phacoemulsification had a better visual outcome and fewer postoperative complications than pars plana lensectomy/vitrectomy in patients with Behçet's disease.

Adult↗

Validation of methods for the assessment of cataract progression in the Roche European-American Anticataract Trial (REACT)

The Roche European-American Anticataract Trial (REACT) will assess the effect of antioxidants on progression of cataract in humans. This report evaluates the methods used in REACT. Seventy three subjects (139 eyes) with cortical (C), posterior subcapsular (P), nuclear (N) or mixed cataract were seen twice within two weeks for eye examinations, assessments of visual function, lens photographs and CCD images. The degree of cataract and nuclear color (NC) were assessed with subjective (LOCS III) and objective (computerized, CASE 2000 CCD) methods. Repeat visit values were used to calculate intraclass correlation coefficients (r1) and 95% tolerance limits (TL). A clinically significant change (CSC) was defined as one step in LOCS III. The relative power of each method to detect cataract change and sample sizes needed to achieve statistically significant results were calculated. The r1 values for visual function tests ranged from 0.76 to 0.88; if these tests of visual function were used to detect a clinically significant change in cataract severity, sample sizes of 840 to 2707 per group would be needed. The r1 values for LOCS III were 0.88 to 0.97, and sample sizes ranged from 50 to 135 per group. The r1 values for the CCD were 0.93 to 0.98, and sample sizes ranged from 1 to 42 with poorer values relating to measurement of P. We conclude that the methods used in REACT are reproducible. The analytical algorithms in the image analysis programs did not permit differentiation between C and P opacification; therefore, P cataract is best measured with LOCS III. REACT sample sizes are adequate to detect a difference of 0.2 LOCS III units/year between the mean rates of cataract progression in two groups.

Adult↗

Accumulation and aberrant modifications of alpha-crystallins in anterior polar cataracts.

Crystallins are the major proteins found in the lens, and the localization of specific crystallins is well known. Overexpression and accumulation of alphaB-crystallin has been observed in response to stress conditions or in certain diseases, such as brain tumors and neurodegenerative diseases. The purpose of this study was to examine whether alpha-crystallins are modified during pathological myofibroblastic changes in lens epithelial cells. Lens epithelial cells attached to the anterior capsules of patients with nuclear or anterior polar cataracts were analyzed quantitatively for alpha-crystallin proteins and mRNAs using Western blot and RT-PCR analysis., respectively. The degree of modification of alpha-crystallins was determined by 2-dimensional gel electrophoresis followed by Western blotting. Higher molecular weight protein bands that were immunoreactive to anti-alphaA- and anti-alphaB-crystallin antibodies around 45 kDa accumulated more in the anterior polar cataract samples than in those with the nuclear type of cataracts. Also monomeric alphaB-crystallins accumulated more in lens epithelial cells of patients with anterior polar cataracts. By comparison, no significant changes were found in the levels of the mRNAs encoding alphaA- and alphaB-crystallins in the different types of cataracts. Both alphaA- and alphaB-crystallin proteins seemed to undergo more extensive modification in anterior polar cataracts. Conclusion. In addition to fibrotic changes, which accompany increased levels of extracellular matrix molecules, accumulation and abnormal modification of alpha-crystallins might be implicated in the pathogenic mechanism of this type of cataract.

Adult↗

Congenital cataract: etiology and morphology.

In a study of congenital cataract in northern India, 76 patients (146 eyes) were evaluated for morphological patterns and etiology. Partial cataracts were found to be three times more common than total cataracts, the lamellar types being the most common among the partial cataracts. Hereditary cataracts had a 19.7% incidence. The majority (46.05%) of cases of congenital cataract were of idiopathic origin. A few cases were associated with metabolic disorders (Marfan's and Marchand's). Strabismus and nystagmus were the most common associated ocular abnormalities (28.94% and 15.79%), and mental retardation was the most commonly associated systemic abnormality. Rubella cataract was seen far less frequently than expected.

Abnormalities, Multiple↗

Cataract and ocular hypertension in children on inhaled corticosteroid therapy.

PURPOSE: To ascertain the incidence of posterior subcapsular cataract and ocular hypertension in a cohort of children < or = 12 years on inhaled steroid therapy. PATIENTS AND METHODS: In this prospective study, a detailed history regarding corticosteroid therapy was obtained for children attending an asthma clinic. The presence and type of lens changes (cataract) was recorded and intraocular pressure (IOP) was measured. The children underwent another eye examination 2 years later. RESULTS: Ninety-five patients were enrolled in the study. Mean patient age was 7 +/- 3 years, and mean duration of inhaled steroid therapy was 2 +/- 1 years. Thirty-six percent of patients received inhaled steroids exclusively, 61% received inhaled steroids with a short course of oral steroids, and 3% received inhaled steroids with a long course of oral steroids. Only 3 (3%) patients had cortical changes that were not visually significant, and none had posterior subcapsular or nuclear cataract. There was no significant differences between children with cataract and those without cataract with respect to age; duration of asthma; and duration, average daily dose, and cumulative dose of inhaled steroids. IOP ranged from 11 to 20 mm Hg (mean, 16 +/- 3 mm Hg). None of the children had ocular hypertension or glaucoma. Ninety patients underwent eye examination 2 years later; none was found to develop posterior subcapsular cataract or increased IOP. CONCLUSION: This study indicates the use of inhaled steroids in children with asthma is probably safe as far as not inducing posterior subcapsular cataract or ocular hypertension.

Administration, Inhalation↗

Human lens epithelial layer in cortical cataract.

Normal and cataractous human eye lenses were studied by morphology and protein analysis. A marked decrease in protein sulfhydryl (PSH) and nonprotein sulfhydryl (NSPH) was observed in nuclear and cortical cataractous epithelia. Moreover, decrease in PSH contents and an increase in insoluble proteins were found to be correlated only in cortical cataractous epithelium which is also accompanied by various morphological abnormalities. In nuclear cataractous epithelium, however, there was very little insolubilisation of proteins. The epithelial morphology in nuclear cataracts was almost similar to normal lens epithelium. Hence, it is assumed that the protein insolubilisation and various morphological abnormalities are characteristics of cortical cataractous epithelium. This leads us to believe that opacification in cortical cataract might initiate in the epithelial layer.

Adult↗

Cataract extraction and lens implantation with and without trabeculectomy: an intrapatient comparison.

OBJECTIVE: To determine whether cataract extraction and lens implantation combined with trabeculectomy provides better long-term results than cataract extraction and lens implantation alone in a group of patients with primary open-angle glaucoma and cataract randomly selected to receive surgery with trabeculectomy in one eye and without in the other. METHODS: A prospective, randomized clinical trial involving 35 patients with bilateral symmetric primary open-angle glaucoma and visually disabling cataracts with procedures performed by a single surgeon in a private practice setting with follow-up for more than 5 years in all cases. RESULTS: After an average of 87 months of follow-up, cataract extraction and lens implantation reduced intraocular pressure 4.4 mm Hg, reduced number of medications by 1.28, increased diopter vector of astigmatism by 1.49, and was associated with visual field loss in 6 of 35 eyes. After an average of 80 months of follow-up, cataract extraction, lens implantation, and trabeculectomy reduced intraocular pressure 8.2 mm Hg, reduced number of medications by 1.76, increased diopter vector of astigmatism by 1.14, and was associated with visual field loss in 1 eye. Both groups had similar improvement in visual acuity and perioperative complications. CONCLUSIONS: Extracapsular cataract extraction, lens implantation, and trabeculectomy is a complex procedure that was beneficial in the long-term control of intraocular pressure and in prevention of visual field loss. This procedure should be considered in patients who may not be able to comply with a complex medical regimen, in whom pressure elevation in the immediate postoperative period would be undesirable, or in whom long-term pressure control at a lower level would be beneficial in preventing further optic nerve damage.

Aged↗

Diabetic cataracts: different incidence between dogs and cats.

Diabetes mellitus is one of the most common endocrinopathies in the dog and cat. Diabetic cataract primarily affects the canine species and is rarely observed in the cat. It has been proposed that the incidence of cataracts in diabetic dogs is high because many of these patients have significant hyperglycemia despite insulin therapy. Age, gender, levels of serum glucose (before and during insulin therapy) and cataract formation were evaluated, retrospectively, in 23 dogs and 22 cats with diabetes mellitus. In the canine population, the groups with the highest frequency of presentation were females and sexually intact animals. In contrast, males and neutered animals were the most prevalent groups in the feline diabetic population. Over 80% of diabetic cats and dogs were older than 7 years. Our results confirm the almost total lack of cataracts in diabetic cats, while they were present in more than half of the dogs. A relation between the incidence of cataracts and the correspondent level of hyperglycemia in the canine and feline species could not be established. The estimation of the relative risk for the development of cataracts in diabetic dogs shows that some population groups have a higher probability for suffering from this ocular alteration. A relation between relative risk and the correspondent level of hyperglycemia in the various groups was not found. This fact indicates that other factors are involved in the unequal appearance of diabetic cataracts in dogs and cats.

Age Distribution↗

Susceptibility to TGFbeta2-induced cataract increases with aging in the rat.

PURPOSE: Cataract is the most common cause of blindness in the world today, and yet there is no generally accepted treatment other than surgical intervention. Studies in rodent models designed to increase understanding of the molecular basis of cataract have shown that transforming growth factor (TGF)-beta induces morphologic and molecular changes similar to those associated with some forms of human cataract. Because aging is the most widely recognized risk factor for cataract, it is important that any animal model be examined in this context. This was a study of the effects of aging on susceptibility to TGFbeta-induced cataract. METHODS: Lenses from weanling, adult, and senile rats were cultured in defined serum-free medium with a range of concentrations of TGFbeta2. The lenses were cultured for up to 7 days, photographed daily, fixed, and prepared for histology and immunolocalization. Opacification was quantified by image analysis. RESULTS: Lenses from weanling, adult, and senile rats all underwent similar cataractous changes when exposed to TGFbeta. This included opacification, the formation of anterior subcapsular plaques, and accumulation of type I collagen and alpha-smooth muscle actin. Lenses from adult and senile animals, however, were generally more adversely affected by TGFbeta than lenses from weanlings. This study also showed that a low dose of TGFbeta administered over a prolonged period had an effect similar to that of a higher dose administered over a shorter period. CONCLUSIONS: An elevation of TGFbeta activity, either acute or chronic, and/or an age-related increase in lens cell susceptibility to TGFbeta may be triggering factors in the etiology of certain forms of cataract.

Actins↗

Outcome of high-volume cataract surgery at an academic hospital.

OBJECTIVE: This study aimed to review the results of high-volume cataract surgery performed at Umtata General Hospital, an academic hospital, during an 'eye surgery camp' held over a weekend. SUBJECTS AND DESIGN: Ninety-eight cataract operations were performed over 3 days at Umtata Hospital during an eye camp to reduce backlog of cataract surgery in the Eastern Cape. After media announcement, patients were selected for cataract surgery and comprehensive pre-operative evaluation was done. Three qualified surgeons operated on the patients. OUTCOME MEASURES: Patients were reviewed at day 1 and at 3- and 6-week intervals in order to study the outcome of such operations. RESULTS: A total of 92.4% of patients achieved visual acuity of 6/60 or better at 6 weeks postoperatively. The surgical complication rate was minimal and overall satisfactory surgical outcome was observed in these cases. CONCLUSION: Teaching hospitals with dedicated ophthalmic operating facilities can be utilised for high-volume cataract surgery over designated short-term periods and can provide a good alternative to mobile eye camp surgery. Until primary and secondary care facilities are optimal for cataract screening and surgery, such camps are recommended to reduce backlog of cataract surgery in the country.

Academic Medical Centers↗

[A study on lens epithelial cell ultrastructure in rhesus monkey cataract].

OBJECTIVE: To investigate the ultrastructure of lens epithelial cells of normal eyes and cataractous eyes in rhesus monkeys. METHODS: Anterior capsules were taken from 4 normal lenses and 4 cataractous lenses of rhesus monkey eyes, and the samples were observed under transmission electron microscope. RESULTS: The ultrastructure of the cataractous lens epithelial cells changed obviously. Mitochondria with disappearance of crista were swollen, and vacuolar. Hollow cell with a single large vacuole in the cytoplasm could be seen. The cytoplasm presented dissolution. Cells were swollen and damaged, even cell membrane disruption could be seen. Karyopyknosis, nuclear deformity, disappearance of perinuclear cistern and nuclear pores could be found. The heterochromatin was concentrated and aggregated at the nuclear periphery. CONCLUSIONS: The ultrastructural changes of the lens epithelial cells in monkey cataractous lens are similar to that in human cataractous lens. Rhesus monkey cataract may be a suitable experimental model to investigate the formation of human cataract.

Animals↗

[Preliminary results of foldable intraocular lens implantation in children with cataract].

OBJECTIVE: To evaluate the result of phacoemulsification and foldable intraocular lens implantation (IOL) through a small incision in children with cataract. METHODS: Phacoemulsification with anterior vitrectomy and foldable IOL implantation in the capsular bag was performed in 37 eyes of 28 children aged 3 - 15 years (mean 7 years), including 27 eyes of congenital cataract and 10 eyes of traumatic cataract. The visual acuity, corneal curvature and possible complication were followed up for 10 months (range, 3 - 15 months). RESULT: The best corrected visual acuity (BCVA) of congenital cataract were all >/= 0.1, and 59.3% >/= 0.5. All the BCVA of cases with traumatic cataract >/= 0.3, and 80% >/= 0.5. The surgically induced astigmatism (SIA) was (1.18 +/- 0.65) D, (0.67 +/- 0.59) D and (0.60 +/- 0.39) D in one week, one month, and three months respectively after the operation, and it was stable in the postoperative one month. Secondary cataract occurred in 5 cases (13.5%), and no other complications were found. CONCLUSIONS: Phacoemulsification and foldable IOL implantation through a small incision in children with cataract can reduce early post-operative astigmatism and shorten the period of visual rehabilitation. It is a safe procedure with milder inflammatory reaction and less complication.

Adolescent↗

[Character of alpha-crystallin molecular chaperone activity in selenite cataract].

PURPOSE: To evaluate the character of alpha-crystallin molecular chaperone activity in selenite cataract. METHODS: alpha-Crystallin from lenses of normal young rats and lenses with selenite cataract were separated and purified by gel filtration chromatography. The chaperone activity of alpha-crystallin was assayed by mearsuring heat-induced aggregation and scattering of catalase. RESULTS: alpha-Crystallin in both normal and cataractous lenses specifically prevented catalase against thermal aggregation compared with control proteins. The preventive ability in alpha H-crystallin was less than in alpha L-crystallin. Chaperone activity was diminished in selenite cataract. There was statistically significant difference in chaperone activity between normal and cataractous lenses in both alpha H-crystallin and alpha L-crystallin respectively. CONCLUSION: The reduction of alpha-crystallin chaperone activity in selenite cataract by preventing thermal aggregation of catalase is an important process in cataract formation.

Animals↗

Cost-effectiveness analysis of cataract surgery: a global and regional analysis.

OBJECTIVE: To estimate the population health effects, costs and cost effectiveness of selected cataract surgery interventions in areas of the world with different epidemiological profiles. METHODS: Effectiveness estimates are based on a review of the literature taking into account factors such as operative failure, complications and patient non-compliance. A population model was applied to follow the lifelong impact on individuals having cataract surgery. Costing estimates are based on primary data collected in 14 epidemiological subregions by regional costing teams and on a literature review. Costings were estimated for different geographical coverage levels using non-linear cost functions. FINDINGS: Intra- and extra-capsular cataract surgeries are cost-effective ways to reduce the impact of cataract-blindness. Extra-capsular cataract surgery is more cost-effective than intra-capsular surgery in all regions considered. Providing extra-capsular cataract surgery to 95% of those who need it (95% coverage level) would avert over 3.5 million disability-adjusted life years (DALYs) per year globally. The cost-effectiveness ranges from 57 International dollars (1 dollar) per DALY in the WHO South-East Asia Region where there is high overall child and adult mortality to 1 dollar 2307 per DALY in the WHO Western Pacific Region where there is low overall child and adult mortality. CONCLUSION: Extra-capsular surgery for cataracts at a high level of coverage is the most cost-effective way of restoring sight in all epidemiological subregions considered. Analysts from countries within a region are encouraged to further contextualize the results based on their own country's specific parameters.

Cataract Extraction↗