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PubMed1991

Rodent models of congenital and hereditary cataract in man.

Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.

Animals↗

PubMed1990

Elemental distribution in frozen-hydrated rat lenses with galactose cataract.

The elemental distributions in frozen-hydrated rat lenses with galactose cataract were compared before and after the onset of the nuclear cataract to investigate the possible role of ion levels in the lens opacification due to the phase separation of the lens cytoplasm. The maps of the weight concentrations of the minor elements, S, Cl, K and Ca, on the basis of wet weight in the central plane of lens were obtained by X-ray analysis with the high energy ion microprobe at a resolution of 50 microns. Before the onset of the nuclear cataract, the distributions of Cl and K, were almost normal, except in the lens posterior periphery with high Cl and low K. In the lens with the nuclear opacity, sudden changes were observed. The Cl increased throughout the lens, and K decreased throughout the lens except at lens anterior thin layer. However, the totalized monovalent ion level changed only slightly. The Ca level increased throughout the lens after the onset of the nuclear cataract, suggesting a possible role of Ca in the nuclear opacification of galactose cataract of rats. The distributions of S were similar to the protein density distributions previously known both in the normal and in the cataractous lenses.

Animals↗

PubMed1990

Characterization of water-insoluble proteins in normal and cataractous human lens.

The mechanism of lens protein aggregation with age and/or cataract formation was investigated using the peptides resolubilized from the insoluble protein fraction of normal and cataractous human lenses. The insoluble fraction was treated with reductants for cleaving disulfide bonds, or with chelating agents for removing calcium ions from the aggregates. This study demonstrates that the insoluble protein aggregates consist of an approximately 400 Kd complex, which is formed by the peptides with lower molecular weight. Protein aggregation in the cataractous lens might be caused by disulfide bonds whereas, in aging, the aggregate might be preferentially formed by calcium ion bridges rather than by disulfide bonds. It was observed that the aggregate from the cataractous lenses involved a peptide with a molecular mass lower by 1 Kd or 2 Kd than the peptides found in the normal lens. The composition of crystallins in aggregating proteins and their secondary structures were also different in the normal and the cataractous lenses. Such changes of molecular weight, conformation, and/or crystallin species in the lens may lead to the disintegration of the orderly arrangement of crystallins, resulting in the diffused reflection and lens opacities which are seen in senile cataract.

Aged↗

PubMed1990

[Detection of sorbitol content in crystalline lens of normal rats and rats with diabetic cataract by 1H-NMR].

The pulse Fourier NMR was employed to measure the artificial diabetic cataract lens at various stages of its formation, and the lenses of the normal rats. Data obtained by using this method show that all the peaks that of water concentrate in the range of delta less than 4 ppm. The peak value at delta = 3.20 ppm is on a marked increase during the formation of cataract which is caused by the phosphate metabolites, such as GPC, ATP, ... etc, in cataract lens. With the development of the disease, the peak width at delta = 3.73 ppm becomes greater and greater, which shows that the activity of sorbitol dehydrogenase has decreased. This leads to a high concentration of the sorbitol in the cataract lens. Consequently, the osmosis pressure in the cataract lens is increased, and excessive water might dip into the crystalline lens to keep the balance of the osmosis pressure. And this might result in the hydration of the fiber cell of the crystalline lens, which might cause a swelling or blisters. These results are in favour of the prolongation of the relaxation time of cataractous lens reported in our other papers, and also support those gained by biochemical studies issued in the medical literature.

Animals↗

PubMed1989

Humoral and cellular immune responses to lens protein in patients with congenital cataract.

In order to understand the immune responses to lens protein in patients with congenital cataract, the passive hemagglutination assay for humoral immunity and the leukocyte migration test for cellular immunity to lens protein were performed on 43 patients with congenital cataract and 30 healthy persons served as control. The results showed that there was no significant difference in the incidence of humoral immune responses to lens protein between patients with congenital cataract and the controls (P greater than 0.05), but the incidence of cellular immune responses to lens protein in patients with congenital cataract was higher than that of the controls (P less than 0.005). The results of this study suggested that during the development of congenital cataract, lens protein leaked into the aqueous humour and entered the systemic circulation, sensitizing lymphocytes and producing cellular mediated immune responses. Further investigation is necessary to determine whether there is any relationship between the immune responses to lens protein and the formation of congenital cataract.

Adolescent↗

PubMed1989

[A cataract classification and grading system].

A cataract classification and grading system developed for cataract epidemiological survey was introduced. Cataractous opacities were classified into cortical, nuclear and subcapsular types. Gradings of cataract progression were divided into early (Grade I), moderate (II) and advanced (III) stages. The grading of cortical opacity was judged by the opaque area in a maximally dilated pupillary zone of which findings were obtained from a red-reflex image. The grading of nuclear opacity was judged from the intensity of scattering light at the nucleus. Three grading steps were based on the densitometrical analysis of photographed images. Subcapsular opacities were classified into three gradings by extensions up to the normal, moderately dilated and maximally dilated pupil size. Regarding cortical and unclear cataracts, standard images indicating border findings between Grades I and II and Grades II and III were provided to help with classification. Nuclear coloration was classified into pale yellow, yellow, brownish yellow and brown including reddish brown and black brown. To document cataractous findings, a recording chart was made.

Cataract↗

PubMed1985

Medical therapy in the prevention of cataract.

Medical treatment of cataract depends on understanding the mechanism of cataract formation. This is established in sugar cataract, in which sugar is metabolised to sugar alcohol. Sugar alcohol accumulates and the resultant osmotic stress is considered to cause lens fibre damage. The conversion of sugar to alcohol is effected by the enzyme aldose reductase and interest now centres around the use of aldose reductase inhibitors. A controlled clinical trial into the effect of the spirohydantoin Sorbinil in adult diabetic cataract has started at Oxford. Aldose reductase inhibitors may also act on non-diabetic cataract, which is supported by some clinical evidence. The biochemical basis of this and other possible treatments for cataract are outlined.

Adult↗

PubMed1983

Na,K-ATPase in simulated eye bank and cryoextracted rabbit lenses, and human eye bank lenses and cataracts.

In the rabbit, cryoextraction of the lens and subsequent storage in Tyrode's solution did not alter the Na,K-ATPase activity from that determined in immediately excised rabbit lenses. Similarly, the procedures employed with the rabbit eye to simulate collection and storage of normal human eyes (eye banking) had no effect upon the Na,K-ATPase activity of the lens. These results permitted the investigation of human lenses with the knowledge that measured Na,K-ATPase activity had not been altered grossly by any manipulation procedures. Analysis of Na,K-ATPase activity in 44 eye bank lenses, 14 primary nuclear cataracts, 11 primary cortical cataracts, 18 primary posterior subcapsular cataracts, and 31 mixed cataracts revealed no significant difference in the enzyme activity between these groups. Similarly, there was no correlation between electrolyte levels and Na,K-ATPase in a further 18 mixed cataracts. It is concluded that, despite an often pronounced electrolyte imbalance, human cataract can develop without significant alteration in Na,K-ATPase activity.

Adenosine Triphosphatases↗

PubMed1981

Supplementing glucose metabolism in human senile cataracts.

Assay of the activities of hexokinase, phosphofructokinase, and pyruvate kinase showed that the first two declined in aging human lens cortex and all three enzymes retained constant activities in the epithelium throughout life. Moreover, both clear and cataractous aging lenses contained the same enzyme activities. ATP contents in cataracts, however, were lower than in clear lenses; in fact, after incubation at 37.5 degrees C in isotonic (290 to 300 mOsm), glucose-containing media, ATP was rapidly lost from cataracts (but not from clear lenses), suggesting excessive ATP expenditure in cataracts for osmotic balance. Cataracts incubated in media containing either glucose-6-phosphate or fructose-1, 6-diphosphate produced significantly higher ATP than with glucose in the media, indicating that glucose metabolism in human senile cataracts could be supplemented with hexose phosphates. Fructose-1, 6-diphosphate appeared to be more efficient than glucose-6-phosphate in preventing lens swelling during incubation.

Adenosine Triphosphate↗

PubMed1984

The effects of image degradation by cataract on vernier acuity.

The resistance of certain types of hyperacuity tasks (eg, vernier acuity) to optical degradation of the retinal image has been demonstrated previously. This suggests that such a task might provide a means of filling the clinical need for a reliable test of retinal function in the presence of cataracts and other ocular opacities. In the present study, we measure several aspects of vernier acuity performance in cataract patients. These data provide an early basis for the development of a vernier acuity test to detect retinal/neural visual loss prior to cataract surgery. We report the results of measurements in 15 cataract patients using a two-dot vernier acuity task with variable separation between the two dots (gap). The data indicate that the shape and mean level of the vernier threshold-versus-gap function co-vary with the functional severity of the opacity as corroborated by Snellen acuity measures. Furthermore, the optical effects of the cataracts we studied are very similar to the effects of degrading the visual stimulus by interposing ground glass for a normal observer. We conclude that the shape of the vernier threshold-versus-gap function is a good indicator of the functional severity of the cataract in patients with otherwise normal vision.

Aged↗

PubMed1978

Experimental cataract production by high frequency ultrasound.

In vivo animal experiments were performed to study the cataractogenic effects of high-frequency, high-intensity ultrasound. A series of anesthetized rabbits was insonified with quantified exposures of ultrasound using a 9.8 MHz focused ultrasonic beam. Ophthalmoscopic and slit lamp examinations revealed small haze cataracts as the first stage of lenticular damage. Larger exposures produced totally opaque cataracts. These first appeared as fine white threads surrounded by haze cataracts. The intensity-exposure time conjugates required to produce haze cataracts were determined over times ranging from 35 msec to 5 sec. At short times (under 100 msec) a relatively constant amount of energy was needed for cataract production. At longer times, the requried energy progressively increased. This observation, together with the physical appearance of these cataracts, suggests that those lesions are the result of thermal phenomena.

Animals↗

PubMed1981

Posterior subcapsular cataracts induced by topical corticosteroids following keratoplasty for keratoconus.

Posterior subcapsular cataracts studied in 86 eyes of 86 patients transplanted for keratoconus were retrospectively studied. The follow-up period ranged between one and four years with a median of 18 months. Twenty-eight eyes developed posterior subcapsular cataracts. The development of posterior subcapsular cataracts was significantly related to the total cumulative steroid dose and the total time steroids were administered (p less than 0.01). Age, surgical technique, and rejection episodes could not be significantly correlated with development of a posterior cataract. The progression of the cataract appeared to be slow, and if topical steroids were discontinued the lens changes appeared to stabilize and progressed in only one patient. The effect of an early posterior subcapsular cataract on visual acuity was minimal in the early stages.

Administration, Topical↗

PubMed1980

Experimental posterior subcapsular cortical cataracts caused by vincristine sulfate.

A typical posterior subcapsular cortical cataract was successfully induced in an organ culture of a rat crystalline lens with the addition of 2 X 10(-5)M vincristine sulfate. A similar cataract was also induced by applying microtubule inhibitors such as Colcemid, colchicine, and podophylotoxin. In a posterior subcapsular cortical cataract induced by vincristine sulfate, metaphase arrest was observed both in the organ culture and cell culture of the epithelial cells. The result indicated microtubule inhibition. The findings illustrated such pathological processes as disturbance of the elongation of epithelial cells, development of vacuolar degeneration and Morgagnian droplets in the spaces between lens fibers, and the appearance of cellular debris due to degeneration of the terminals of the lens fibers as a result of microtubule inhibition. Apart from findings in sugar cataracts, sequential changes of cataract development did not include fluctuations of the lens water content up to the 7th day (immediately prior to the development of nuclear cataracts).

Animals↗

PubMed1995

Optimal temporal frequencies in oscillatory movement hyperacuity measurements of visual function in cataract patients.

Hyperacuity tasks have been suggested for the assessment of potential visual function in the presence of cataracts. To test this suggestion, hyperacuity thresholds for an oscillating bar were measured in 30 subjects with idiopathic cataract and in 24 age-matched normals over a range of oscillation frequencies. Each subject's cataract was categorized using the Oxford Clinical Cataract Classification and Grading System. Cataract was found to have a significant effect on thresholds, although a differential morphological effect on thresholds was equivocal. Thresholds at higher temporal frequencies were significantly raised when compared to the normal group. The main conclusion to be drawn from this study is that motion hyperacuity thresholds appear unaffected by cataract at low oscillation frequencies and should be used in preference to higher frequencies in the assessment of such patients.

Aged↗

PubMed1994

Management of monocular cataract with long-term dilation in children.

We describe the use of long-term dilation and patching therapy in the management of three cases of pediatric monocular cataract. The cataracts were felt to be visually significant in the undilated state but consistent with good formed vision in the dilated state. One patient had a congenital cataract managed from 4 weeks of life, and two patients had late diagnosed cataracts of indeterminate onset presenting with dense deprivation amblyopia. The congenital cataract patient ultimately demonstrated recognition acuity of 20/40, and both the older children ultimately demonstrated an acuity of 20/30. We recommend considering long-term dilation and conventional amblyopia therapy rather than lensectomy in such cases if the cataract is felt to be consistent with development of good formed vision in the dilated state.

Amblyopia↗

PubMed1993

Activity loss of glutathione synthesis enzymes associated with human subcapsular cataract.

PURPOSE: To assess the activities of the two enzymes required for glutathione synthesis, gamma-glutamylcysteine synthetase and glutathione synthetase, in various forms of human cataracts. METHODS: The Cooperative Cataract Research Group cataract classification method and standard enzyme assay procedures were used. RESULTS: An inverse relationship was shown between residual activity of each of the glutathione synthesis enzymes and degree of subcapsular cataract. A weaker inverse relationship existed between glutathione synthetase activity and supranuclear and nuclear cataracts. No other parameters yielded comparable correlations with the activity of either enzyme. CONCLUSIONS: Activity loss of the glutathione synthesis enzymes is associated with human subcapsular cataract formation.

Aged↗

PubMed1994

[The lipoproteins in human diabetic cataract].

Four kinds of lipoproteins contained in human diabetic cataract lens were separated by of sequential flotation in an ultracentrifuge, and the quantities of each were determined by selective precipitation. Chylomicron, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) were separated from cataract lenses as lipoprotein fractions, and quantified. Chylomicron was present in the largest quantity among the four. There was no significant difference between the total amount of lipoprotein contained in diabetic cataract lenses (96.95 +/- 4.03 micrograms/lens) and that in senile cataract lenses (89.51 +/- 8.35 micrograms/lens). The quantities of VLDL and LDL, however, were significantly larger in diabetic cataract lenses (14.84 +/- 0.55 and 20.97 +/- 0.58 micrograms/lens, respectively) than in senile cataract lenses (6.30 +/- 0.46 and 7.45 +/- 0.61 micrograms/lens, respectively). We demonstrated histologically that LDL receptors are localized on the lens epithelium and its underlying layer.

Aged↗

PubMed1993

[Magnetic resonance imaging study on rat sugar cataract].

Proton nuclear magnetic resonance (1H-NMR) is one of the most important methods for noninvasively evaluating the state of water in the biological system. It could be useful for evaluation of the early changes of cataract. In this study, in vivo magnetic resonance imaging (MRI) was applied to rat galactosemic cataract, which is a model of the human diabetic cataract, and compared with the histological findings. The relationship between the relaxation times (T1, T2) and the water contents were discussed. The T1 and T2 values were prolonged and the high intensity area of the lens cortex was enlarged from the early stage of the cataract (two days after the intake of galactose). These changes preceded the histological changes. This suggests that MRI is applicable for the evaluation of anti-cataract agents, for example aldose reductase inhibitors, against human diabetic cataract.

Aldehyde Reductase↗