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PubMed1996

Skin disease and age-related cataract.

Dermatological conditions and treatments were analysed in a study comparing cataract patients and stringently matched controls. One thousand patients were taken from the cataract waiting list of a specialist eye hospital. For each patient a matched control of the same gender, half-decade of age, and family doctor but without cataract was selected. Venepunctures and eye examinations were performed on both patients and controls; in addition, questionnaire information was obtained from each. Age-related cataract is significantly associated with dermatological abnormality and its treatment, the former association being more significant and more pronounced after 69 years of age. The association of hydrocortisone use after 69 years of age and cataract, however, remains significant even after adjustments for dermatological abnormality and steroid use, suggesting that even among steroid medications hydrocortisone is particularly strongly associated with cataract.

Adult↗
PubMedDate not supplied

Slitlamp assessment of age of onset and incidence of cataracts in pink-eyed, tan-hooded retinal dystrophic rats.

Posterior subcapsular cataracts (PSC) are associated with hereditary retinal dystrophy in the Royal College of Surgeons (RCS) rat model and with human retinitis pigmentosa. The relationship of lens and retinal pathology has never been explained. Previous studies of pink-eyed RCS rats aged 2.5 to 11 months had shown an incidence of cataract of 24% when observed by the unaided eye and 60% by direct ophthalmoscopy, while 40% of rats were considered to have clear lenses. Unlike the retinal degeneration, which appeared in all homozygous animals, cataract seemed not to be predictably associated with the rdy mutation. To test this further, we studied the lenses of rats of different ages with a diagnostic slitlamp. We confirmed that by 8 to 15 months of age, rats fed a diet containing recommended concentrations of all known nutrients for rodents developed cataracts with an incidence of 23% when observed by unaided eye. In addition, opacities were seen in 74% with the indirect ophthalmoscope and 20 D lens; but 100% had at least a "sugar grain" type PSC by slitlamp. The slitlamp-detectable cataract was first seen in some animals by 49 days, and by 56 days all rats examined had bilateral PSC. This is an age at which the rod photoreceptors have degenerated. We concluded that slitlamp-detectable PSC are predictably associated with the retinal dystrophy of the rdy mutation. The RCS rat model may be relevant to a type of retinal degeneration having a constant association of cataract.

Age Factors↗
PubMed1984

Oxidative stress on lens and cataract formation: role of light and oxygen.

The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.

Animals↗
PubMed1984

Conformational changes in soluble lens proteins during the development of senile nuclear cataract.

Soluble crystallins were isolated, by gel filtration, from the nucleus and cortex of types I-IV cataractous lenses and neonatal lenses. Extinction coefficients were determined and used to calculate the proportion of the crystallins. alpha Crystallins were the major proteins in the cortex of the cataractous lens whereas beta crystallins predominate in the nucleus and in the neonatal lens. Electrophoretic and immunological data, indicated that there was very little soluble gamma crystallin in the cataractous tissue. Highly specific competitive radioimmunoassays were used to estimate the crystallin contents of the various extracts. Values obtained for the neonatal extracts agreed closely with those from gel filtration but, in general, the values found for the cataractous proteins were low. The immunological reactivity of beta crystallin decreased progressively with the development of nuclear colour whereas alpha crystallin reactivity decreased sharply with the onset of nuclear cataract (type II lens) and then partially recovered. No significant alterations were found in the micro-environments of tryptophan residues in any of the proteins indicating that there are no gross conformational changes in the soluble proteins during cataract development. It would appear that the losses of immunochemical reactivity are due to chemical and/or conformational alterations which are restricted to the surface of the protein molecules.

Aged↗
PubMed1987

Physical properties of membranes and membrane lipids from the fiber cell of the U18666A-cataractous rat.

Steady state fluorescence anisotropy of parinaric acid probes was used to examine lipid motion in membranes and membrane lipids from U18666A-induced cataractous rat lenses. Cortical and nuclear fractions were examined separately. The drug treatment resulted in an increase in the sterol/phospholipid ratio in the nucleus and a decrease in this ratio in the cortex. Fluorescence anisotropy of trans parinaric acid (tPnA) suggested that membranes from the cortex of cataractous lenses were more ordered than the cortical membranes from control or treated-but-clear lenses. Membranes from the nucleus of control lenses were more ordered than membranes from the cortex of controls. Nuclear membranes from cataractous lenses were slightly less ordered than nuclear membrane from control or treated-but-clear lenses. Similar experiments using liposomes prepared with membrane lipid from lens cortex showed that membrane lipids from treated lenses, control lenses, and treated-but-clear lenses had similar fluorescence anisotropy profiles, suggesting that cortical lipids had similar order. Conversely, fluorescence anisotropy of parinaric acid probes in liposomes prepared from nuclear fractions showed a slight increase in lipid order from control to treated-but-clear to cataractous preparations. These results are interpreted to indicate the presence of an alteration in lipid-protein interactions in cortical membranes in the cataractous lenses; this results in more ordered membranes at the physiological temperature in these lenses. The increase in the order of cortical membranes from cataractous lenses is dependent on the presence of membrane proteins rather than lipids, since it is not seen in the liposome preparations (which are protein-free).(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenes↗
PubMed1989

Lens crystallins in aqueous and vitreous humor in selenite overdose cataract.

The purpose of this research was to determine if crystallins were released from the lens into the aqueous and vitreous humor in selenite-overdose cataract. At 20 days post injection, aqueous and vitreous were obtained from lenses containing nuclear cataract or "mature" cataract (nuclear and cortical opacities). Humors were analyzed by direct ELISA and immunoblotting using antibodies against lens crystallins. Both types of selenite cataract showed increased alpha-, beta- and gamma-crystallins in aqueous and vitreous. Increases in crystallins in vitreous humor were larger than in aqueous humor, possibly because of slower turnover of vitreous. Extensive membrane damage in selenite cataract probably caused leakage of crystallins from the lens to aqueous and vitreous humors. This model may be useful for studies on the immunologic response of the body to lens crystallins released by cataract.

Animals↗
PubMed1993

DNA single strand breaks in human lens epithelial cells from patients with cataract.

In recent years, there has been renewed interest in the association between DNA damage to the lens epithelium and the development of lens opacities. Although a number of in vitro studies have indicated that lens epithelial cells are susceptible to a variety of DNA damaging insults and that these cells possess the capacity to repair such damage, no previous studies have directly addressed whether DNA damage is associated with human cataract in vivo. Utilizing samples of lens epithelial cells obtained from patients undergoing cataract surgery, the percentage of cells containing DNA single strand breaks was directly determined by the single-cell gel assay (SGA) method. Non-cataractous human Eye Bank lenses of similar ages to the cataractous samples and calf lenses were used as controls. In approximately 50% of the cataractous samples analyzed, the proportion of cells containing DNA single strand breaks was significantly higher than in control lenses. No relationship between age and DNA damage was noted. These findings are consistent with the hypothesis that in some human patients with cataract, DNA damage in the lens epithelial cell population may be related to the development of lens fiber cell opacity.

Aged↗
PubMed1995

Proteolysis by calpain is an underlying mechanism for formation of sugar cataract in rat lens.

To confirm the effect of a new aldose reductase inhibitor (ARI), rat lenses were cultured with xylose. ARI prevented opacities and reduced lens hydration caused by xylose. Next, cataract was produced by feeding a diet containing 50% galactose. ARI was tested for amelioration of cataract. On day 19 after feeding of galactose, nuclear cataracts were visible in 75% of the animals receiving only galactose, while nuclear cataracts were not observed in animals treated with ARI. In galactose cataract, lens hydration and calcium were significantly increased. Calpain in soluble and insoluble fractions was decreased. Alpha- and beta-crystallins were proteolyzed. These changes were inhibited by administration of ARI. These results suggested that proteolysis by calpain is an underlying mechanism in formation of sugar cataract in rat lens.

Aldehyde Reductase↗
PubMed1996

Fiber cell morphology and cytoplasmic texture in cataractous and normal human lens nuclei.

PURPOSE: The goal of this study was to compare the ultrastructure of the oldest cells in opaque and transparent human lenses. METHODS: Age-related nuclear cataracts, late-onset diabetic nuclear cataracts and normal aged lenses were examined by transmission electron microscopy. Cross-sectional profiles of fiber cells in the embryonic, fetal and juvenile nuclear regions were obtained to facilitate direct comparisons between lens regions and between sample groups. Image analysis was performed to determine cross-sectional areas of fiber cells in each region. RESULTS: The average cross-sectional area increased approximately sixfold from the outer to the inner nuclear regions in all lenses measured. In each nuclear region, fiber cells displayed a characteristic size, shape, arrangement and type of interdigitations which were consistently seen in all the lenses examined. Some lenses had more complex interdigitations than others. Gap junctions were identified as pentalamellar structures having 16 nm width and appeared identical throughout the nuclei of both normal and cataractous lenses. The cytoplasm of all lenses was smooth and free of large density variations. However, the cytoplasm of some cataractous lenses appeared more granular in texture than noncataractous lenses. Cellular degeneration, debris or large cellular defects were not seen in the cores of cataractous lens nuclei. CONCLUSIONS: These results indicate that only minor ultrastructural differences exist between the oldest fiber cells in normal and cataractous lenses, and that the presence of extensive cellular damage and disruptions is not necessary for the generation of nuclear opacities in aged lenses. Our observations suggest that light scattering sufficient for vision impairment may involve structural alterations much smaller than previously proposed.

Aged↗
PubMed1994

Risk factors for cortical, nuclear, posterior subcapsular and mixed cataract: a case-control study.

A case-control study was conducted to evaluate risk factors for cortical, nuclear, posterior subcapsular and mixed cataract. The 385 cases and 215 controls (age range 40-75 yrs) included in the study underwent a complete ophthalmological examination and laboratory blood tests, and were interviewed about behavioral variables, environmental exposure and their medical history. Lens opacity was classified using the 'Lens Opacity Classification System II' (LOCS II). On multivariate analysis, the risk factors for cortical cataract were the presence of diabetes for more than five years (OR = 3.7) and increased serum K+ and Na+ levels. A history of surgery under general anesthesia and the use of sedative drugs were associated with reduced risk (OR = 0.4). Posterior subcapsular cataract was associated with the use of steroids (OR = 18.2) and diabetes (OR = 8.1), and nuclear cataract with calcitonin (OR = 5.7) and milk intake (OR = 0.25). Mixed cataract was associated with a history of surgery under general anesthesia (OR = 0.5). Some of these results are consistent with the findings of similar studies performed in different geographical areas, others are not. The results suggest a possible role of electrolyte imbalance in the development of senile cataract.

Adult↗
PubMed1996

Visual acuity disturbance in subjects over 50 years of age in a population-based cataract survey.

Visual acuity is still an essential examination item in cataract epidemiological studies, even though this parameter lacks objective reliability. A population-based epidemiological study was conducted in a rural area of Japan to find out the relationship between visual acuity levels and cataracts, the types of gradings of which were evaluated by an objectively reliable method through lens images, and to serve as a sample for researchers who perform epidemiological studies on cataract but lack the latest methodology. 863 participants above 50 years of age were examined and those previously diagnosed with ocular diseases which affect visual acuity were excluded from the analysis as much as possible. The mean visual acuity (LogMAR) in subjects in their 50s, 60s, 70s and over 80 years of age was 1.1, 1.0, 0.7 and 0.4, respectively. Both the mean and the distribution of visual acuity showed a statistically significant relationship to ageing (p < 0.01, p < 0.01). Both age and cataract grading showed a statistically significant relationship to visual acuity (p < 0.01), but there was no significant interaction effect between these two variables upon visual acuity. Visual acuity worsened remarkably with ageing in the eyes with grade III, whereas that of eyes with grades I and II remained fairly stable at a level of 0.7-1.0, except for those above 80 years of age. A fairly good visual acuity of 1.0, 0.8 and 0.7 remained in the eyes with pure cortical cataract of grades I, II and III, respectively, whereas those with mixed type cataract were 0.9, 0.6 and 0.3, respectively.

Aged↗
PubMed2005

Temporal relationship between lens protein oxidation and cataract development in streptozotocin-induced diabetic rats.

We compared the progression of lens opacification with the time course of oxidation of lens proteins under conditions of streptozotocin-induced experimental diabetes in rats. By the end of the 17th week, approx. 50% of the diabetic animals developed mature cataracts. During the following month, 95% of the eyes in the diabetic group became cataractous. In the course of lens opacification we observed a time-dependent increase in the content of protein carbonyls and decrease in the concentration of protein sulfhydryls in the lenses of diabetic animals. Significantly higher protein carbonyl (p<0.01) and lower protein sulfhydryl (p<0.001) content was found in lenses with the advanced stage of cataract when compared with the diabetic lenses still transparent. We showed that the values of protein carbonyls exceeding 1.2 nmol/mg protein and of sulfhydryls falling below 60 nmol/mg protein corresponded to an approximately 50% incidence of mature cataract development. At the end of the 34th week, when all lenses of diabetic rats became cataractous, the corresponding values of protein carbonyls and sulfhydryls were 2.5 nmol/mg protein and 27 nmol/mg protein, respectively. The main finding of this study is the disclosure of quantitative relationship between the degree of protein oxidation and the rate of advanced cataract development in the widely used model of streptozotocin-induced experimental diabetes in rats.

Animals↗
PubMedDate not supplied

Thyroid eye disease presenting after cataract surgery.

Strabismus presenting after cataract surgery has been attributed to a variety of disorders, some of which are unrelated to the surgery. When thorough ophthalmologic and neurologic examinations fail to elucidate a definitive etiology, the motility disturbance is often ascribed to operative trauma to the orbital soft tissues. In a series of 58 patients with strabismus presenting after cataract surgery, eight (14%) were found to have previously unsuspected thyroid eye disease. Three of the eight patients had past histories of systemic dysthyroidism, but none reported diplopia prior to cataract extraction. Three of the remaining five patients showed normal thyroid function tests. Absence of diplopia prior to cataract extraction in these patients may be due to: 1) poor vision precluding diplopia until surgical restoration of sight; 2) intraoperative aggravation of the inflammatory process in otherwise subclinical thyroid eye disease; or 3) onset of clinical thyroid eye disease that was temporally associated with cataract surgery by chance. Thyroid eye disease should be included in the differential diagnosis of all patients presenting with binocular diplopia following cataract surgery. Suitable neuroimaging studies may be needed to confirm the diagnosis.

Aged↗
PubMed1999

Deamidation of alpha-A crystallin from nuclei of cataractous and normal human lenses.

PURPOSE: To quantitate the extent of deamidation of asparagine-101, glutamine-50, and glutamine-6 of alpha-A crystallin in the nucleus from human cataractous and normal lenses. METHODS: Reverse phase chromatography was used to prepare alpha-A crystallin from total proteins of the nucleus from cataractous and age-matched normal human lenses. Synthetic peptides were made corresponding to the expected amidated and deamidated tryptic fragments containing asparagine-101, glutamine-50, and glutamine-6. The peptides were used to identify and quantitate amidated and deamidated forms of tryptic fragments from alpha-A crystallin eluting from a reverse phase column. RESULTS: Significant amounts of deamidation of asparagine-101 and glutamine-50, but not glutamine-6, were present in alpha-A crystallin from nuclear sections of both cataractous and age-matched normal lenses. Quantitative analysis of tryptic peptides containing these residues indicated no statistical difference in deamidation in cataractous versus normal lenses. CONCLUSIONS: There was no significant difference in the extent of deamidation of asparagine-101, glutamine-50, and glutamine-6 for alpha-A crystallin, purified from the nucleus of cataractous versus age-matched normal lenses. These results strongly suggest that deamidation of these residues does not play a role in the biogenesis of human nuclear cataract.

Aged↗
PubMed1998

Risk factors for cataract: a case control study.

The present study was designed as a hospital-based, group-matched, case-control investigation into the risk factors associated with age-related cataract in central India. The study included 262 cases of age-related cataract and an equal number of controls. A total of 21 risk factors were evaluated: namely, low socioeconomic status (SES), illiteracy, marital status, history of diarrhoea, history of diabetes, glaucoma, use of cholinesterase inhibitors, steroids, spironolactone, nifedipine, analgesics, myopia early in life, renal failure, heavy smoking, heavy alcohol consumption, hypertension, low body mass index (BMI), use of cheaper cooking fuel, working in direct sunlight, family history of cataract, and occupational exposure. In univariate analysis, except marital status, low BMI, renal failure, use of steroids, spironolactone, analgesics, and occupational exposure, all 14 other risk factors were found significantly associated with age-related cataract. Unconditional multiple logistic regression analysis confirmed the significance of low SES, illiteracy, history of diarrhoea, diabetes, glaucoma, myopia, smoking, hypertension and cheap cooking fuel. The etiological role of these risk factors in the outcome of cataract is confirmed by the estimates of attributable risk proportion. The estimates of population attributable risk proportion for these factors highlight the impact of elimination of these risk factors on the reduction of cataract in this population.

Aged↗
PubMed1999

Mortality rates after cataract extraction.

Senile cataract may be a marker of generalized tissue aging. We examined this hypothesis using population-based linked health data. We hypothesized that any such association would diminish with increased use of cataract surgery. Mortality rates of those 50-95 years of age undergoing cataract surgery in British Columbia during either 1985 or 1989 were compared with the provincial population of comparable age who did not undergo cataract surgery during the study period. The 1985 cohort included 8,262 patients undergoing surgery and a comparison population of 804,303, and the 1989 cohort included 11,952 patients and a comparison population of 839,393. Using Cox regression, for the 1985 cohort, the hazard ratios for dying during follow-up were 3.2 for males 50-54.9 years of age [95% confidence limits (CL) = 2.0, 5.0] and 3.3 for females (95% CL = 1.9, 5.7). Hazard ratios for older age groups decreased with age. We also fit an additive risk model that produced excess mortalities that were less age dependent. In the 1985 analysis, these ranged from +7.1 per 1,000 (95% CL = +0.44, +13.76) to +20.3 (95% CL = +13.24, +27.36) for males and -17.5 (95% CL = -28.28, -6.72) to +2.0 (95% CL = -2.12, +6.12) for females. Findings for the 1989 analyses were similar, indicating that the association between cataracts and generalized aging remained constant despite a large increase in the use of cataract surgery.

Age Distribution↗
PubMedDate not supplied

Inappropriateness of cataract extraction: an analysis in two Israeli hospital settings.

OBJECTIVE: To assess and compare the appropriateness of cataract extraction in two Israeli regional hospitals. SETTINGS: Two Israeli hospitals located in different geographic areas. DESIGN: A randomized sample of 150 patients was drawn from a list of all patients who underwent cataract surgery at the two study hospitals during 1995. Detailed extraction of hospital medical records was performed. The appropriateness of cataract surgery was assessed using the Medical Review System, an interactive expert system that assesses the appropriateness of selected medical and surgical procedures. RESULTS: The rates of cataract surgery in the two hospitals were 0.54 and 0.59 operations per 1,000 population, respectively, and the age-adjusted rates per 1,000 population were 5.7 and 6.2, respectively. The percentage of patients with only light perception or hand-motion perception in the operated eye before the operation was 62.2%, with no difference in the two hospitals. There was not a significant difference in the distribution of visual acuity before the operation; however, there was a significant difference in the distribution of visual acuity after the surgery. Rates of inappropriate surgeries in the two hospitals were found to be similar to the inappropriate rate in the United States (1.3%). The preoperative visual acuity of patients undergoing cataract surgery in Israel was inferior to the visual acuity of patients undergoing cataract surgery in the United States. CONCLUSION: To increase quality and cost-effectiveness in the Israeli medical system, future studies of this type are warranted in connection with surgical procedures.

Cataract Extraction↗
PubMed1999

[Cathepsin A activity in the aqueous humor in patients with cataract, absolute glaucoma and intraocular tumors].

PURPOSE: To evaluate cathepsin A activity in the aqueous humor of patients with cataract, absolute glaucoma and intraocular tumors. MATERIAL AND METHODS: The studies were performed on human aqueous humor taken from anterior chamber of eye balls of patients operated because of cataract, absolute glaucoma and intraocular tumors. Cathepsin A activity was determined by the ninhydrin method with synthetic substrate (N-Cbz-Phe-Ala) at its optimum pH 5.0. RESULTS: In the human aqueous humor of the eye with cataract cathepsin A activity was more than three times higher than in the eye with choroid tumors and absolute glaucoma. No differences of enzyme activity in aqueous humor between patients with glaucoma and intraocular tumors were found. CONCLUSION: The increasing proteolytic activity of cathepsin A in aqueous humor of patients with cataract suggests its importance in cataract pathogenesis. This implies that cathepsin A is involved in development of lens opacity and is found in the aqueous humor due to diffusion from cataractous lens in which the proteolytic process prevails.

Aqueous Humor↗