Alteration of cadherin in dexamethasone-induced cataract organ-cultured rat lens

PURPOSE: A side effect associated with long-term treatment of various diseases with steroids is a high incidence of posterior subcapsular cataracts (PSC). To understand the mechanism underlying steroid-induced cataract, the cultured lens model was developed, and the expression of potential candidate proteins during opacity formation was examined. METHOD: Rat lenses were carefully dissected from the surrounding ocular tissue and incubated in medium 199. Dexamethasone was then added to the medium. The lenses were cultured for 7 days and photographed daily to record the development of opacity. Differential expression of candidate proteins was examined by Western blot analysis. RESULT: Various degrees of opacity were observed on the posterior subcapsular region as early as 5 days after incubation with dexamethasone. The expression of E-cadherin and N-cadherin decreased in the cultured rat lenses during the development of opacity. CONCLUSIONS: The pattern of opacity that developed in cultured rat lenses closely resembled that observed in patients with PSC. The results suggest that the decrease in E-cadherin plays a role in the formation of steroid-induced cataract.     

Changes in cytoskeletal proteins in childhood cataract lenses

Purpose: Approximately 50% of congenital and childhood cataracts seen in the clinic is of undetermined origin. Biochemical analysis of the cataracts is rare. This study analyzes lens proteins to determine the mechanism of congenital and childhood cataracts. Method: We analyzed the lens proteins from 10 young patients after cataract operations, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), densitometry analysis, and Western immunoblotting.Results: Densitometry of separated proteins showed a decrease in the high molecular protein bands of posterior subcapsular cataract (PSC). Specifically, spectrin (235 kDa), filensin (100 kDa), and vimentin (57 kDa) were absent from the SDS-PAGE of PSC. Increases in filensin and vimentin were observed in a Christmas tree cataract and lamellar cataracts. Western immunoblots confirmed the densitometry of SDS-PAGE.Conclusion: These results suggest that changes in cytoskeletal proteins may contribute to congenital and childhood cataracts.     

Changes in cytoskeletal proteins in childhood cataract lenses]

PURPOSE: Approximately 50% of congenital and childhood cataract seen in the clinic is of undetermined origin. Biochemical analysis of the cataracts is rare. This study analyzes lens proteins to determine the mechanism of congenital and childhood cataracts. METHOD: We analyzed the lens proteins from 10 young patients after cataract operations, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), densitometry analysis, and western immunoblotting. RESULTS: Densitometry of separated proteins showed a decrease in the high molecular protein bands of posterior subcapsular cataract (PSC). Specifically, spectrin (235 kDa), filensin (100 kDa), and vimentin (57 kDa) were absent from the SDS-PAGE of PSC. Increases in filensin and vimentin were observed in a Christmas tree cataract and lamellar cataracts. Western immunoblots confirmed the densitometry of SDS-PAGE. CONCLUSION: These results suggest that changes in cytoskeletal proteins may contribute to congenital and childhood cataract.     

Cataracts in the aging rat lens. Morphology and acid phosphatase histochemistry of incipient forms

The present investigation deals with morphological and certain histochemical changes that precede and accompany cataracts associated with aging in the rat. The cataracts were of two types: supranuclear (SNC) and posterior subcapsular (PSC). The initial biomicroscopie lesions, which were associated with the auterior and posterior lens suture systems, respectively, were attributed to cytological alterations of the ends of the superficial fiber cells. Cortical alterations common to both types of cataract included segmental cellular swelling, and the formation of assorted globular and multilamellar inclusions. With SNC, large multilamellar bodies corresponded to anterior sutural vacuolar opacities; while swelling and dissociation of the fiber cell bodies were associated with the formation of lamellar separations, lesions which eventually appeared in the peripheral cortex. Posterior subcapsular intercellular vacuoles, many of which developed a lamellated outer structure, were characteristic of the early form of PSC.An acid phosphataso which served as a marker for lysosomal hydrolases was demonstrated in the intercellular spaces of lenses with early forms of degeneration. The major source of the extracellular enzyme appeared to be the Golgi/lysosomal system within the epithelium and cortex, although the cortical smooth endoplasmic reticulum was not ruled out.Our studies support the concept that the swelling and degeneration of cortical fibers occurring in the initial stages of the cataracts might have been caused by intercellularly located hydrolases. The value of the aged rat lens as a model for human senile cataract was reinforced by the many similarities between the murine and human forms of the disease.     

Anterior subcapsular plaque cataract in hyperornithinaemia gyrate atrophy--a case report.

Hyperornithinaemia gyrate atrophy (HOGA) is a rare autosomal recessive disorder in which chorioretinal degeneration occurs with cataracts, myopia, and hyperornithinaemia. We report the case of an 18-year-old female who presented with the typical features of HOGA, including posterior subcapsular cataracts and elevated plasma ornithine. She later developed distorted vision in both eyes owing to wrinkling of the anterior lens capsules. Histological examination following lens extraction showed the wrinkling was caused by focal distortion from capsular fibrosis (anterior subcapsular plaque cataract). This specific lens change has not been linked previously with HOGA.     

Aberrant lens fiber differentiation in anterior subcapsular cataract formation: a process dependent on reduced levels of Pax6

PURPOSE: TGFbeta can induce development in lenses of opaque subcapsular fibrotic plaques that have many features of human subcapsular cataracts. To understand further the events associated with the onset and progression of TGFbeta-induced cataract, several different models for anterior subcapsular cataract (ASC) were used and characterized. METHODS: Anterior subcapsular plaques were induced in rat lenses cultured with TGFbeta and in transgenic mice overexpressing TGFbeta in the lens. ASC was also examined in lenses of mice haploinsufficient for Pax6, as well as in human biopsy specimens. Immunofluorescence and in situ hybridization labeling were used to examine changes in patterns of gene expression associated with cataract formation in these models. RESULTS: Examination of TGFbeta-induced cataract in transgenic mice established that the subcapsular plaques are composed of a heterogenous cell population: a population of myofibroblastic cells as well as a population of lens-fiber-like cells. Further support for phenotypic change comes from the observation that the cells in these plaques no longer expressed lens epithelial markers, such as Pax6 and Connexin43. Subsequent examination of human biopsy specimens of ASC, as well as lenses from Pax6-deficient mice, showed that the anterior subcapsular plaques in both cases were also composed of a heterogenous population of cells. In contrast, anterior subcapsular plaques that developed in vitro in response to TGFbeta did not have this same cellular heterogeneity, as no fiber-like cells were present. CONCLUSIONS: These findings suggest that in vivo, during TGFbeta-induced cataract formation, some lens epithelial cells transform into myofibroblastic cells, whereas others differentiate into fiber cells. As this pathologic change is accompanied by altered expression of genes characteristic of the normal lens epithelial cell phenotype and as lenses from Pax6-deficient mice exhibit development of anterior subcapsular plaques closely resembling those induced by TGFbeta in transgenic mice, the authors propose that a reduction in Pax6 levels may be essential for this pathologic process to progress. Furthermore, it is clear from these in vitro studies that TGFbeta alone cannot reproduce the same morphologic and molecular changes associated with ASC formation in vivo, indicating that additional molecule(s) in the eye are important in this process.     

Human Cataracta Complicata: Clinicopathologic Correlation

Complicated cataracts of the posterior subcapsular zone may be associated with a number of systemic conditions. Cataracts from patients with retinitis pigmentosa, Turner's syndrome, myotonic dystrophy, or those who were taking corticosteroids were examined clinically and pathologically after intracapsular cataract extraction. Two major types of posterior subcapsular opacities were observed: one type had multiple vacuoles, while the other type was a more solid appearing (plaque-like or snowball) opacity clinically. The predominant morphologic counterpart (by light and electron microscopy) of the vacuolar opacity is liquefactive necrosis with aberrantly migrated epithelial cells growing into the cataract. In the plaque-like or snowball opacity, the lens fibers are generally disorganized into round globules. The clinical significance is that the vacuolar-liquified posterior subcapsular cataract may be more easily removed by extracapsular methods than the plaquelike opacity; however, the proliferative cells in the vacuolar type are probably the source of an after-cataract membrane that may require discission.     

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.     

Diabetes, cardiovascular disease, selected cardiovascular disease risk factors, and the 5-year incidence of age-related cataract and progression of lens opacities: the beaver dam eye study

PURPOSE: To describe the relationships of diabetes mellitus, cardiovascular disease, and selected cardiovascular disease risk factors to cumulative incidence of age-related cataract and to progression of lens opacities over a 5-year interval.METHODS: A follow-up examination of the Beaver Dam Eye Study cohort was performed 5 years after the baseline evaluation. Ages at the census prior to baseline ranged from 43 to 84 years of age. Protocols for examination, lens photography, and grading were the same for both examinations.RESULTS: Age at baseline was the most significant characteristic associated with incidence of nuclear, cortical, and posterior subcapsular cataract in those without diabetes (P < .001) for all cataracts. The positive association of age with cataract was found for nuclear and cortical cataract in the worse eye (P ≤ .04) but not posterior subcapsular cataract in those with diabetes. Progression of nuclear sclerosis was common, occurring in about 70% of subjects when considering either eye. Incident cortical and posterior subcapsular cataracts (P ≤ .001 for worse eye for each lesion) and progression of cortical and posterior subcapsular opacities were more common in those with diabetes (P ≤ .001 for either eye for each lesion). Increased glycated hemoglobin level was associated with increased risk of nuclear and cortical cataracts in those with diabetes. Relationships of risk factors to posterior subcapsular cataracts, especially among those with diabetes, were often in the expected direction but lacked significance possibly due to small samples.CONCLUSIONS: Diabetes mellitus is associated with incidence over 5 years of cortical and posterior subcapsular cataract and with progression of more minor cortical and posterior subcapsular lens opacities. These changes may be related to level of glycemia. Cardiovascular disease and its risk factors have little effect on incidence of any age-related cataract.     

Cataracts induced by microwave and ionizing radiation

Microwaves most commonly cause anterior and/or posterior subcapsular lenticular opacities in experimental animals and, as shown in epidemiologic studies and case reports, in human subjects. The formation of cataracts seems to be related directly to the power of the microwave and the duration of exposure. The mechanism of cataractogenesis includes deformation of heat-labile enzymes, such as glutathione peroxide, that ordinarily protect lens cell proteins and membrane lipids from oxidative damage. Oxidation of protein sulfhydryl groups and the formation of high-molecular-weight aggregates cause local variations in the orderly structure of the lens cells. An alternative mechanism is thermoelastic expansion through which pressure waves in the aqueous humor cause direct physical damage to the lens cells. Cataracts induced by ionizing radiation (e.g., X-rays and gamma rays) usually are observed in the posterior region of the lens, often in the form of a posterior subcapsular cataract. Increasing the dose of ionizing radiation causes increasing opacification of the lens, which appears after a decreasing latency period. Like cataract formation by microwaves, cataractogenesis induced by ionizing radiation is associated with damage to the lens cell membrane. Another possible mechanism is damage to lens cell DNA, with decreases in the production of protective enzymes and in sulfur-sulfur bond formation, and with altered protein concentrations. Until further definitive conclusions about the mechanisms of microwaves and ionizing radiation induced cataracts are reached, and alternative protective measures are found, one can only recommend mechanical shielding from these radiations to minimize the possibility of development of radiation-induced cataracts.     

The concept of corticosteroid cataractogenic factor revisited

Formation of posterior subcapsular cataracts is a known complication of systemic corticosteroid therapy. However, the relation between steroid dosage, cumulative dose and type of steroid on one hand and the subsequent formation of cataract on the other is unclear. We carried out a study to determine the incidence of posterior subcapsular cataracts in 64 children who had undergone renal transplantation and to attempt to determine what factors were associated with cataract formation. Cataracts were detected in 17 (26%) of the patients. The steroid dosage, cumulative dose and duration of therapy were not associated with cataract formation. There was a significant difference in the distribution of HLA-CW3 antigen between the patients with cataracts and those without cataracts. The reason for the link between corticosteroid therapy and formation of posterior subcapsular cataracts remains unclear.     

Functional vision with cataracts of different morphologies: comparative study

PURPOSE: To evaluate the influence of cataract morphology on the functional vision of patients with age-related cataract and normal macular function and compare subjectively perceived functional impairments to distance visual acuity, reading acuity, and maximum reading speed between cataract types. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: Seventy-five patients awaiting first-eye cataract surgery were asked to characterize their visual difficulties in everyday life using a German version of the VF-14 questionnaire. Cataracts were categorized and graded using the Lens Opacities Classification System III. Monocular and binocular visual acuity and reading performance were determined in randomized order. RESULTS: There were significant differences in functional vision between nuclear cataracts and posterior subcapsular cataracts (PSC); the VF-14 score and the self-reported visual satisfaction were significantly lower in PSC patients (P<.05). Posterior subcapsular cataracts significantly increased self-reported impairment in distance and near vision, although the visual acuity was comparable to that in the other groups (P =.9). Significant differences in functional vision were also seen between PSC and nuclear-cortical cataracts (P<.05). No significant differences in functional vision were found between nuclear cataracts and nuclear-cortical cataracts (P>.05). CONCLUSIONS: The VF-14 questionnaire reliably evaluated functional differences caused by different cataract morphologies; these differences were underestimated when only visual acuity was measured. Patients with PSC had increased functional impairment, indicating that cataract surgical intervention is indicated at an earlier stage in these patients. The significant differences between the morphological types of cataract should be taken into consideration when the benefit of cataract surgery is to be measured on the basis of functional improvement.     

Cataract in retinitis pigmentosa. An analysis of cataract surgery results and pathological lens changes

The result of cataract surgery and lens pathoanatomical examination were presented in patients with retinitis pigmentosa (RP). A retrospective study of 24 cataract extractions in 15 RP patients was carried out, with special regard to visual outcome and surgical complications. The results were compared to an age matched randomly selected control group. In the retinitis pigmentosa group the post-operative visual acuity was generally good, and the surgical complications except for one case of central venous thrombosis were not more frequent than in the control group. Seven lenses from 5 patients with RP were analysed using transmission electron microscopy and quantitative microradiography. In the lenses with a progressive subcapsular edema, extensive extracellular vacuolization was found in the lens epithelium. Focal degeneration of epithelial cells was seen both in the more stationary posterior subcapsular cataracts and the progressive subcapsular cataracts. Different degrees of mitochondrial swelling was found in the epithelial cells of the stationary cataracts. The subcapsular lens fiber changes consisted of an extensive swelling of hydrated cells together with a significant reduction in their dry mass content. Migrating elongated nuclei-containing cells were found on the posterior capsule in both stationary and progressive cataracts.     

The comparability of estimates of retroilluminated lens opacities as judged from film-based and digital imaging

PURPOSE: Neitz film-based retroillumination cameras, the standard for documenting retroilluminated lens opacities for epidemiologic studies, are no longer produced. A digital imaging system is now available for imaging these opacities. We sought to compare gradings of images from both systems. DESIGN: Comparison of technique. METHODS: One hundred fourteen lenses were imaged with both systems and graded according to protocols. Concordance between the methods was compared using kappa statistics. RESULTS: There was moderate concordance for cortical opacities (kappa = 0.63) and good concordance for posterior subcapsular opacities (kappa = 0.83). Grades from digital images slightly underestimated the frequency and severity of cortical cataract. CONCLUSION: Digital imaging of retroilluminated lens opacities results in similar classification of the severity of opacities. It will be useful for epidemiologic studies of cortical (CC) and posterior subcapsular cataracts (PSC).     

Relation of ocular trauma to cortical, nuclear, and posterior subcapsular cataracts: the Beaver Dam Eye Study

BACKGROUND: The consequences of minor ocular trauma in the general population are unclear. The relation of self reported ocular trauma to cortical, nuclear, and posterior subcapsular cataracts is described in a defined population. METHODS: Population based, cross sectional study involving all people aged 43 to 86 years, living in Beaver Dam, Wisconsin (n=4926). Ocular trauma was ascertained by interview and cataract was graded from lens photographs. The relation of ocular trauma to cortical, nuclear, and posterior subcapsular cataracts was examined. RESULTS: People with a history of ocular trauma were more likely to have cortical (odds ratio (OR): 1.5; 95% confidence interval (CI): 1.0 to 2.2) and posterior subcapsular (OR: 1.7; 95% CI: 1.0 to 3.1) cataracts, compared to people without a history of trauma. These associations were stronger for people with previous trauma caused by a blunt object (OR: 3.3; 95% CI: 1.6 to 6.9 for cortical cataract, and OR: 4.1; 95% CI: 1.5 to 10.8 for posterior subcapsular cataracts). However, in analyses comparing the frequencies of cataract between traumatised and non-traumatised eyes among people with unilateral ocular trauma, the ocular trauma association for cortical cataract was no longer present, although the association for posterior subcapsular cataract persisted (OR: 2.4; 95% CI: 0.8 to 7.8). CONCLUSION: The data provide evidence of a possible association between self reported ocular trauma and posterior subcapsular cataract.     

Assessment of contrast sensitivity. Part II: The relationship between objective lens opacity and laser interferometric contrast sensitivity in the cataract patient

The laser interferometer can effectively bypass the optics of the eye and measure retinal function in patients with immature cataracts. However, it is not known how much laser interferometric measurements are impaired by cataract density. In this study we compared objective lens opacity using the IntraOptics opacity lensmeter with contrast sensitivity (CS) measured by a Randwal He-Ne laser interferometer. Comparison of lens opacity with CS in the cataract population revealed an inverse linear relationship between objective lens opacity and retinal contrast sensitivity. Separation by cataract type showed correlation coefficients as high as -0.91 for nuclear sclerotic predominant cataracts and as low as no significant correlation for posterior subcapsular predominant cataracts. Comparisons of before and after implantation surgery contrast sensitivities (as measured by the laser interferometer) with preoperative lens opacities (as measured by the IntraOptics opacity lensmeter) quantified the extent to which laser interferometric measurements underestimated potential retinal function. We found that for all cataracts, other than posterior subcapsular predominant cataracts, potential contrast sensitivity (in decibels) was underestimated by about 0.2 to 0.3 times the opacity measured by this technique.     

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.     

Early development of selenium-induced cataract: slit lamp evaluation

The purpose of our research was to document early lenticular changes preceding cataract formation in rats receiving an elevated dose of selenium. The following stages were observed after selenium injection: Stage 1 (13-24 hr post-injection), formation of posterior equatorial subcapsular cataract (PESC); Stage 2 (24-72 hr), decline of the PESC, development of a prominent 'washer' shaped change in the refraction of the cortex, and first appearance of swollen fibers around the nucleus; Stage 3 (three to five days), appearance of bilateral dense central nuclear cataracts and further development of perinuclear swollen fibers; Stage 4 (five to 10 days), some nuclear cataracts became more opaque and/or angular. The results are consistent with the hypothesis that the initial site of action of selenium in nuclear cataract formation is not in the lens nucleus. Rather, selenium causes early changes outside the nucleus, which are followed by nuclear cataracts.