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Persistent vertical binocular diplopia after cataract surgery.

PURPOSE: To report the incidence of, and factors associated with, persistent vertical diplopia after cataract surgery. DESIGN: Consecutive interventional case series. METHODS: Retrospectively, all adult patients examined during a five year, five month period because of new onset persistent (>3 months) vertical binocular diplopia after cataract surgery were analyzed. All patients had their cataract surgery at the same outpatient ophthalmic surgery center, and were referred to the author, enabling calculation of incidence. Trends in anesthesia type and strabismus complications therefrom were also assessed. Comparison was made between ophthalmologist-administered retrobulbar anesthesia versus anesthesia staff-administered retrobulbar anesthesia. Incidence during a period in which hyaluronidase was not incorporated in the retrobulbar anesthetic was calculated. RESULTS: Persistent vertical diplopia occurred after cataract surgery in 32 (0.18%) of 17,531 eyes that had cataract surgery. No patient whose cataract surgery was conducted with topical anesthesia (3817 eyes) had persistent vertical diplopia, whereas 32 (0.23%) of the 13714 eyes whose cataract surgery was done after retrobulbar anesthesia were affected. No cases of persistent postoperative diplopia were found among 7410 cataract surgery eyes after retrobulbar injection given by one cataract surgeon. There was a threefold greater number of left eyes involved than right eyes (P <.005). No significant (P >.20) increase in cases of persistent vertical diplopia was noted during a period of hyaluronidase shortage. CONCLUSIONS: In this study, persistent binocular vertical diplopia after cataract surgery occurred in 0.23% of cases in which retrobulbar anesthesia was performed. No cases were found after topical anesthesia. Occurrence may be technique-related.

Aged↗

May nitric oxide molecule have a role in the pathogenesis of human cataract?

Recent studies have shown that nitric oxide molecule may have a role in the development of cataract. In this study, we measured the levels of a nitric oxide metabolite (nitrite) in the cataractous and normal human lenses. A modified Griess assay was used to determine the nitrite levels in the lenses as a measure of nitric oxide, based on the spectrophotometric method. Nitrite was detected in 26 (44.1%) cataractous lenses and was found below the detection limit in 33 (55.9%) cataractous lenses. Mean nitrite levels in cataractous lenses (2.77+/-5.26nmol/100mg) was found higher than the normal lenses (0.77+/-0.79nmol/100mg) but this increase was not statistically significant. Comparison of nitrite levels among lenses with various types of cataracts revealed higher levels in lenses with posterior subcapsular cataracts. Hypertensive patients had also significantly higher nitrite levels in their cataractous lenses. The increased levels in the cataractous lenses display a possible role of nitric oxide in the pathogenesis of cataract in human eyes.

Adult↗

Separation of the yellow chromophores in individual brunescent cataracts.

Quantitative changes in the 330 nm absorbing chromophores and 350/450 nm fluorophores of water-soluble (WS) and water-insoluble (WI) proteins of individual human cataract lenses were characterized and compared with aged normal human lens. Twenty-five brunescent cataract lenses from India were selected from five different stages (types I-V) based upon the color of the lens. The WS and WI proteins from each lens were collected and subjected to an extensive enzymatic digestion procedure under argon. The lens protein digests were separated by Bio-Gel P-2 size-exclusion chromatography and individual peaks were analyzed further by reversed-phase HPLC. The total WI proteins increased and the total WS protein decreased with the development of cataract, especially in the late stages of cataract (III-V). The total 330 nm absorbance and 350/450 nm fluorescence of the WI fraction also increased, however, the A(330) and fluorescence per mg lens protein were constant except for type V (black) lenses. Bio-Gel P-2 chromatography separated the chromophores and fluorophores into four fractions. The main fraction (designated as peak 2+3) from the cataract WI proteins was several times higher than that present in aged normal human lens WI proteins. A significant increase of this fraction was observed in WI proteins, but not in WS proteins with cataract development. Similarly, fractions 1 and 4 in the WI proteins also increased gradually but fraction 5 did not. Reversed-phase HPLC resolved fraction (2+3) of the water-insoluble sonicate supernatant proteins into four 330 nm absorbing peaks and eight fluorescent peaks. Among these peaks, a late-eluting peak (peak 8) increased 10 to 15-fold with the progress of cataract, and accounted for 80% of the total chromophores in type V lenses. This peak may represent limit digests of advanced glycation end-products (AGEs) derived protein cross-links. HPLC profiles of fraction 5 from both WS and WI proteins showed numerous new peaks which were not observed in either WS protein from cataract or WI proteins from aged normal human. The severe coloration and the higher levels of numerous novel chromophores and fluorophores in brunescent cataractous lenses reveal the possibility that a different chemistry occurs during cataract development.

Aged↗

Influence of cyclosporin on steroid-induced cataracts after renal transplantation.

PURPOSE: To study the effect of cyclosporin (CsA) on steroid-induced cataracts in patients following renal transplantation. METHODS: The subjects comprise 140 patients who had undergone renal transplantation at Kanazawa Medical Hospital. These subjects had received ophthalmologic examinations prior to their surgery and subsequently over the span of 12 months following surgery. The charts of these patients were re-examined for this study. The subjects were divided into two groups: the conventional therapy group (Group C) that received azathioprine and methylprednisolone; and the triple therapy group (Group T) that received azathioprine, methylprednisolone, and CsA. There were 73 and 67 patients in Groups C and T, respectively. The cataracts were classified according to Crews' classification. Steroid-induced cataract was diagnosed when vacuoles were observed or opacity was evident in the posterior subcapsular region. Subjects who exhibited any lens opacity before renal transplantation were excluded from this study. RESULTS: The total amounts of systemic steroid administered during the first year and at the final observation period were significantly lower in Group T than in Group C. The prevalence of steroid-induced cataracts of grade 1 and above was 55% and 63% for the first year, 73% and 89% for the second year, 74% and 92% for the third year, and 83% and 96% for the fifth year in Groups C and T, respectively. By the third year, the percentage of subjects exhibiting corrected visual acuity <0.8 or receiving cataract surgery was significantly higher in Group T than in Group C. There was no significant difference in the total dose of steroids, in subjects with cataracts over grade 1 and those with grades 0 and 1, between these groups. In Group C, the total steroid pulse therapy dose was significantly higher in subjects with steroid-induced cataracts over grade 1 than in those with grades 0 and 1. CONCLUSIONS: The observed rate of steroid-induced cataracts increased with the use of cyclosporin, despite a decrease in the total dose of systemic steroids. From this finding we suggest that the additional use of CSA may contribute to the development of steroid-induced cataracts. Steroid pulse therapy is considered a risk factor for the development of steroid-induced cataracts.

Adolescent↗

The effects of simulated cataract on reading with normal vision and simulated central scotoma.

Reading rates are slower for persons with low vision than for normally-sighted persons. This study investigated the change in reading performance and reading eye movements when we simulated the two most common causes of low vision--central field loss and cataract--and their combination (scotoma + cataract). Three subjects read sentences with each of these simulated impairments at five different letter sizes. They required larger letters to read with the cataract or scotoma than they did with normal vision, and larger still to read with scotoma + cataract; the change in eye movements relative to normal vision was similar across conditions. When reading large letters (1.61 degrees), the cataract had almost no effect, while the scotoma and scotoma + cataract reduced reading rate for two of the subjects. The cataract had a greater impact on performance relative to normal vision for these same two subjects, while for the third subject the cataract had a greater impact with the scotoma in place. Cataract extraction tends to be postponed in patients with central field loss because it is not perceived to be beneficial. The findings from this study, as well as others, suggest that patients with central field loss would benefit from cataract extraction.

Adult↗

Autosomal dominant congenital cataract. Interocular phenotypic variability.

PURPOSE: While intrafamilial morphologic heterogeneity of autosomal dominant congenital cataracts has been well established, interocular variation in individual patients of described pedigrees is small. The authors describe a seven-generation family with 48 of 138 individuals known to be affected with autosomal dominant congenital cataracts of the pulverulent type. Affected patients exhibit a seemingly random expression of either unilateral or bilateral lens opacities. METHODS: Ophthalmic and medical histories were obtained, complete ophthalmologic examinations were performed, blood samples were drawn, and transformed lymphoblastoid lines were established on 53 patients. Eighty-five members of the family were unable to be examined. RESULTS: Twenty-eight of the 53 individuals examined had congenital cataracts. Of these patients, 19 eyes (8 right eyes and 11 left eyes) were unilateral and 9 were bilateral. The clinically unaffected eye in patients with unilateral cataracts showed no evidence of lenticular opacity under detailed slit-lamp examination. Severity of the cataracts included a subtle unilateral zonular cataract with 20/20 visual acuity, bilateral inner fetal nuclear pulverulent opacities with 20/16 visual acuity in both eyes, and dense unilateral and bilateral nuclear cataracts requiring early surgical removal. Incorporating the historic data on patients who were not examined, we found 48 affected members (28 unilateral, 17 bilateral, 3 obligate carriers who were not examined). CONCLUSIONS: Hereditary cataracts typically are symmetric in affected individuals. The authors describe a large pedigree with the apparently random expression of an autosomal dominant gene as either unilateral or bilateral cataract. To their knowledge, this is the first such family described in the literature. Currently, work is under way to determine if the causative gene is linked to previously defined cataract loci on chromosomes 1, 2, or 16.

Cataract↗

Cataract development induced by repeated oral dosing with FK506 (tacrolimus) in adult rats.

FK506 (tacrolimus), a potent immunosuppressant, is used for inhibiting allograft rejection in the organ transplantation field. In a preclinical toxicity study in rats, FK506 induced various toxicities, including renal and pancreatic injuries. One of these toxic findings was cataract, and we have found that cataract appeared in rats dosed orally with FK506 for 13 weeks and more. Therefore, to better elucidate the onset mechanism of FK506-induced cataract, we measured biochemical parameters, such as sorbitol, Na,K-ATPase and glutathione in the lens of rats. Rats were dosed with FK506 in oral daily doses of 0.2, 1 or 5 mg/kg for 13 weeks, the lowest dose of which approximated the expected clinical dosage. Cataract developed in the 5-mg/kg/day group, with an incidence of 25%, whereas no cataract formation was observed in the 0.2- or 1-mg/kg/day groups. Five mg/kg/day led an increase of sorbitol and a decrease of reduced type glutathione, but did not affect Na,K-ATPase activity of the lens. FK506 is known to have diabetogenicity mediated through pancreatic injury, which appears as vacuolation of islet cell in rats. Five mg/kg/day of FK506 induced an elevation of blood glucose associated with glucose intolerance, and decrease of both basal insulin level and insulin content in the pancreas, and the changes were in parallel with the cataract development in the present study. On the other hand, diabetic parameters did not change in the 0.2- or 1-mg/kg/day groups. These observation suggest that diabetes developed in the rats dosed with 5 mg/kg/day of FK506. Coadministration of a novel aldose reductase inhibitor, Zenarestat, at an oral dose of 50 mg/kg/day resulted in a reduction of incidence of the FK506-induced cataract and a decrease of sorbitol levels in the lens when compared to that in the lens of rats dosed with 5 mg/kg/day of FK506. These results suggest that FK506-induced cataract in rats is due to an accumulation of sorbitol in the lens, secondary to the diabetogenic effect of FK506. FK506 treatment at the doses of 0.2 and 1 mg/kg/day neither affected parameters indicative of diabetes nor induced cataract in rats, suggesting that the cataract would not develop with FK506 if diabetic parameters were kept under control.

Administration, Oral↗

Cataract after total body irradiation and bone marrow transplantation: degree of visual impairment.

PURPOSE: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. METHODS AND MATERIALS: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow transplantation were analyzed with respect to the degree of visual impairment as a result of cataract formation. The probability to develop severe visual impairment (SVI) was determined for all patients, and the degree of visual impairment was assessed for 56 patients with stabilized cataract, using three categories: no, mild, or severe. RESULTS: For all 93 patients, the probability of developing a cataract causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with steroid treatment (p <0.001). All SVI-free probability curves reached a plateau distinct from the cataract-free curves. Apparently, cataracts developing late in the follow-up period rarely cause SVI. Of the patients with stabilized cataract, 32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild visual impairment was present in 61% of all patients with stable cataract and no steroid treatment compared with only 13% of the patients treated with steroids (p = 0.035). CONCLUSION: SVI occurs in only some of the patients (52%) with stable cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid treatment markedly increases the probability of developing visual problems as result of a cataract after TBI.

Acute Disease↗

Cataract surgery in highly myopic eyes corrected by phakic anterior chamber angle-supported lenses(1).

PURPOSE: To assess the incidence of cataract, potential causes of its development, and the outcome of cataract surgery after previous implantation of phakic angle-supported anterior chamber intraocular lenses (AC IOLs) in highly myopic patients. SETTING: Instituto Oftalmológico de Alicante, Department of Refractive Surgery, Spain. METHODS: Two hundred sixty-three highly myopic phakic eyes of 160 patients had implantation of a phakic AC IOL. Follow-up was up to 8 years (range 38.4 to 103.2 months). Eyes that subsequently developed cataract had cataract extraction and were studied during follow-up for clinical association to other preoperative or postoperative data. Cataract surgery was performed after phakic IOL explantation by phacoemulsification and posterior chamber IOL (PC IOL) implantation (Domilens-Chiron AL3). RESULTS: Nuclear cataract developed in 9 cases (3.42%) a mean of 42.91 months +/- 17.7 (SD) after phakic AC IOL implantation. Final best spectacle-corrected visual acuity (BSCVA) was not significantly different from that after phakic AC IOL implantation (P =.25, paired Student t test). Mean endothelial cell loss after cataract surgery was 6.87% +/- 0.42% cells/mm(2). Age at implantation of older than 40 years and axial length greater than 30. 0 mm were the 2 factors significantly related to nuclear cataract development (r = 1.69 and 1.98, respectively; P <.05). CONCLUSIONS: There is a potential risk of nuclear cataract development after phakic AC IOL implantation to correct high myopia in patients older than 40 years and with very high (greater than 30.0 mm) axial myopia. Phakic IOL explantation, phacoemulsification, and PC IOL implantation successfully resolved this complication. The benefits in terms of BSCVA and spherical equivalent obtained after phakic AC IOL implantation were preserved after cataract surgery.

Adult↗

Pediatric cataract surgery with or without anterior vitrectomy.

PURPOSE: To evaluate after-cataract formation in children having cataract surgery with or without dry anterior vitrectomy and possible differences according to age. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS: This retrospective study comprised 85 eyes of 85 patients from 0 to 15 years old who had cataract surgery with or without anterior vitrectomy after the implantation of an intraocular lens (IOL). All patients had primary posterior capsulorhexis but no optic capture. Thirty-five patients received a heparin-surface-modified poly(methyl methacrylate) IOL (809C, Pharmacia & Upjohn) and 50 patients, a foldable acrylic IOL (AcrySof(R), Alcon). The records from follow-up visits at the patients' home clinics were used for analysis. RESULTS: Significantly fewer children were operated on for after-cataract if they had cataract surgery with anterior vitrectomy (P <.05). This applied to both IOL types. In the children older than 7 years in the AcrySof IOL group, there was no difference in the frequency of after-cataract surgery (P >.05). CONCLUSION: In children younger than 7 years with an AcrySof IOL, the rate of after-cataract surgery was significantly less in those who had an anterior vitrectomy at the time of cataract surgery (P <.05). In younger children, it is advantageous to perform cataract surgery with anterior vitrectomy to help prevent after-cataract formation; however, vitrectomy is not necessary in older children.

Acrylic Resins↗

Expression of protein gene product 9.5 in the anterior lens epithelial cells of atopic cataracts.

PURPOSE: To investigate the mechanisms of atopic cataract by immunohistochemically observing protein gene product 9.5 in lens epithelial cells (LECs) of atopic cataracts. SETTING: Departments of Ophthalmology and Anatomy, Shiga University of Medical Science, Shiga, Japan. METHODS: Specimens of anterior capsule obtained from 6 patients with atopic cataract and 8 patients with senile cataract were stained immunohistochemically and examined by light, electron, and confocal microscopy. RESULTS: In the LECs of the atopic cataracts, the arrangement and cell shape were varied. Immunohistochemistry for protein gene product 9.5 demonstrated selective localization, unlike with senile cataracts. This was especially prevalent in the spindle-shaped cells around the central opaque lesion. Protein gene product 9.5 positive cells overlapped with major basic protein positive cells in the atopic cataracts. CONCLUSIONS: The results indicate that the properties of LECs of atopic cataracts are different from those of senile cataracts. Protein gene product 9.5 and major basic protein seem to be concentrated in atopic cataracts.

Adult↗

Lycopene attenuates oxidative stress induced experimental cataract development: an in vitro and in vivo study.

OBJECTIVES: Lycopene, a nutritional antioxidant, was evaluated for its anticataract potential to further establish its role in cataract prevention. METHODS: The ability of lycopene to modulate the biochemical parameters was investigated by in vitro studies. Enucleated rat lenses were maintained in organ culture containing Dulbecco's Modified Eagles Medium alone or in addition with 100 microM selenite and served as the normal and control groups, respectively. For the test group, the control medium was supplemented with 10 microM lycopene. The lenses were incubated for 24 h at 37 degrees C. At the end of the incubation period, the lenses were examined for morphologic variation, and biochemical parameters such as reduced glutathione, the lipid peroxidation product malondialdehyde, and the antioxidant enzymes glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase were estimated. In vivo selenite cataract was induced in 9-d-old rats by subcutaneous injection of sodium selenite (25 micromoles/kg of body weight). The rats in the test group were injected with lycopene (200 microg/kg body weight, intraperitoneally) 4 h before the selenite challenge. The incidence of cataract was observed when the rats first opened their eyes. Galactose cataract was induced in rats by feeding 30% galactose in the diet. Rats in the test group were fed orally with 200 microg/kg of lycopene daily, and rats in the control group received only vehicle. Cataract stages were graded at regular intervals. RESULTS: A fall (25%) in the glutathione level and a rise (32%) in the malondialdehyde content were observed in control as opposed to normal lenses. Lycopene supplementation in the medium significantly (P < 0.001) restored glutathione and malondialdehyde levels. A significant decrease in the activity of antioxidant enzymes also was observed in the control lenses. A significant restoration in the activities of superoxide dismutase (P < 0.05) and catalase and glutathione S-transferase (P < 0.01), with no effect on glutathione peroxidase, was observed in the lycopene-supplemented group. Lycopene also reduced the incidence of selenite cataract. Only 9% of the eyes in the test group developed dense nuclear opacity as opposed to 83% in the control group. A significant delay in the onset and progression of galactose cataract was observed with oral feeding of lycopene. Only 35% of the eyes developed mature cataract as opposed to 100% in the control group. CONCLUSIONS: Lycopene protects against experimental cataract development by virtue of its antioxidant properties, and it may be useful for prophylaxis or therapy against cataracts.

Animals↗

Effects of cataract type and location on visual function: the Blue Mountains Eye Study.

PURPOSE: To measure the effect of cataract type, severity and location on presenting, and best-corrected visual acuity, contrast sensitivity, and glare disability. METHODS: In all, 3654 (82.4% participation rate) eligible noninstitutionalised residents aged 49 years or older, living in two postcode areas of the Blue Mountains, Australia, received detailed eye examinations including visual acuity, contrast sensitivity, and glare disability testing. Data from right eyes were analysed using multiple regression modelling. RESULTS: The effect of age on visual acuity and contrast sensitivity only became evident in persons aged at least 60 years. Cataract severity was inversely related to visual acuity and contrast sensitivity. Late posterior subcapsular cataract caused the greatest reduction in visual acuity. Early grade cataract caused significant reduction in contrast sensitivity at intermediate and high spatial frequencies, but late grade cataract reduced contrast sensitivity across all spatial frequencies. There was insufficient study power to detect consistent significant effect of cataract on glare disability tests or cortical cataract location on visual function. CONCLUSIONS: Age at least 60 years, cataract type, and cataract severity were principal determinants of visual acuity and contrast sensitivity in this study. Axial and superotemporally located cortical cataract had the greatest effect on visual function tests.

Aged↗

Intravitreal triamcinolone will cause posterior subcapsular cataract in most eyes with diabetic maculopathy within 2 years.

PURPOSE: To determine the incidence of cataract following intravitreal triamcinolone (IVTA) for diabetic macular oedema. METHODS: Prospective, non-randomised, interventional cohort case series. A total of 27 eyes of 27 patients with diabetic macular oedema received an intravitreal injection of 4 mg (0.1 ml) of triamcinolone acetonide inferotemporally through the pars plana under direct vision. In 20 patients the fellow eye served as control, whereas seven patients had both eyes injected (not simultaneously). Seven patients had a repeat (second) injection in the same eye. The main outcome measures were cataract and intraocular pressure (IOP) rise of at least 5 mmHg (IOP responder). RESULTS: The mean follow-up time was 18.9 months (range 13-29 months). A total of 22 (81%) of 27 eyes developed cataract during the follow-up period, of which 20 (74%) were posterior subcapsular in nature. None of the 20 uninjected fellow eyes developed posterior subcapsular cataract. Mean time to cataract formation was 16.2 months. In the seven patients who had both eyes injected, mean time to cataract formation was 16.5 and 17.1 months in the first and second eye, respectively. Mean time to cataract formation in seven eyes receiving a repeat second injection was 17.9 months. There was no significant difference in cataract formation between IOP responders (85%) and non-responders (79%) (P=1.00, Fisher's exact test). Uneventful cataract surgery was performed in six eyes of five patients. CONCLUSION: This study demonstrates that given appropriate long-term follow-up, the majority of patients, even after a single IVTA injection, will go on to develop cataract, of which posterior subcapsular will be by far the most common.

Adult↗

Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins.

BACKGROUND: Age-related cataracts are a major public health problem. The relative importance of genes and environment in the causation of nuclear cataracts, the most common form of age-related cataracts, is not known. METHODS: We studied 506 pairs of female twins (226 monozygotic and 280 dizygotic) who were 50 to 79 years old (mean, 62). The amount of nuclear cataract in the right and left eyes was determined objectively by analysis of Scheimpflug lens photographs (yielding three measures) and subjectively with use of the Oxford Clinical Cataract Classification and Grading System (yielding one measure). All eight measures (four in each eye) were subsequently combined in one summary measure of nuclear cataract for each woman. A univariate maximum-likelihood model was used to estimate the variance of the genetic and environmental contributions to each of the measures. RESULTS: The different measures of cataract formation were highly correlated (correlation coefficients, 0.71 to 0.94). The mean scores were similar for the right and left eyes and for monozygotic and dizygotic twins. Quantitative genetic modeling of each of the nuclear-cataract scores invariably resulted in a best-fitting model that involved additive genetic effects, unique environmental effects, and age. The common environmental and dominant genetic effects could be removed from the models without significant loss of fit. The overall heritability in the combined nuclear-cataract score (the proportion of the variance explained by genetic factors) was 48 percent (95 percent confidence interval, 42 to 54 percent); age accounted for 38 percent of the variance (95 percent confidence interval, 31 to 44 percent) and unique environmental effects for 14 percent (95 percent confidence interval, 12 to 18 percent). CONCLUSIONS: Genetic effects are important even in such a clearly age-related disease as nuclear cataract, explaining almost 50 percent of the variation in the severity of this disease.

Age Factors↗

An estrogen receptor repressor induces cataract formation in transgenic mice.

Despite the high prevalence of age-related cataracts, there are currently no known therapies to delay or prevent their occurrence. Studies in humans and rodent models suggest that estrogen may provide protection against age-related cataracts. The discovery of ocular estrogen receptors (ERs) indicates that estrogen protection may result from direct interactions with its receptors in the eye, instead an indirect consequence from effects on another tissue. Studies in our transgenic mouse model validate the concept that estrogen is beneficial for the eye. These mice express ER Delta , a dominant-negative form of ER alpha that inhibits ER alpha function. In the ER Delta 3 transgenic mice, cortical cataracts spontaneously form in ER Delta 3 females after puberty and progress with age. The cataracts initiate in the equatorial region of the lens where the epithelial cells differentiate into elongating fiber cells. Cataract formation can be prevented if the females are ovariectomized before, but not after, sexual maturity. Both male and female ER Delta 3 mice develop cataracts after neonatal treatment with the potent estrogen diethylstilbestrol (DES). The incidence of spontaneous and DES-induced cataracts in ER Delta 3 mice is 100%, yet these cataracts are absent from the wild-type mice. These data suggest that repression of estrogen action induces cortical cataract formation because estrogen is required to activate the ER Delta 3 repressor. Evidence of DES-induced cataracts in the ER Delta 3 males as well as the females suggests that estrogen is important in lens physiology in both sexes. The ER Delta 3 mice provide a powerful model for assessing the role of estrogen in maintaining the transparency of the lens.

Animals↗

Induction of cortical cataracts in cultured mouse lenses with H-89, an inhibitor of protein kinase A.

PURPOSE: To compare the effects of two serine-threonine protein kinase inhibitors in a mouse lens culture system previously designed to investigate cortical cataracts caused by L-buthionine sulfoximine (BSO), inhibitor of GSH biosynthesis. METHODS: Cataract development in HL-1 medium was evaluated visually or by measurement of lens Na+/K+ ratio through atomic absorption. Protein changes were evaluated by 32P-labeling, 2D-gel electrophoresis, phosphorimaging and mass spectrometry. Results. H-7 (50 microM), inhibitor of protein kinase A (PKA) and protein kinase C (PKC), did not cause cataracts, but inhibited BSO cataract development. By contrast, 25 microM H-89, selective inhibitor of PKA, caused large annular cortical cataracts and 100-fold elevation of Na+/K+ within 30 hr in day 10 lenses, in either the presence or absence of BSO. H-89 cataracts were also seen in day 12 and day 21 lenses. 32P-labeling of day 12 lenses pretreated with H-89 displayed more than 80% decrease in phosphorylation of alphaA crystallin, a known substrate of PKA, in the insoluble protein fraction. 2D-gel electrophoresis of day 12 H-89 cataract lens fractions revealed limited degradation of alpha and beta crystallins, degradation of cytoskeletal proteins, and elevated lens Ca2+ (>4 nmol/mg wet wt.), suggesting Ca2+-activated proteolysis. Conclusions. High Na+/K+ cataracts are induced by H-89, selective inhibitor of PKA, but not by H-7, an inhibitor of both PKA and PKC that impeded BSO-induced Na+/K+ elevation and cataract. These results suggest contrasting effects of PKA and PKC on lens cation transport and cortical cataract development.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Comparing the multifocal electroretinogram topography before and after cataract surgery.

PURPOSE: To investigate whether multifocal electroretinogram (mfERG) topography would be affected by nuclear cataract. METHODS: Multifocal electroretinograms were recorded from 10 elderly subjects (10 eyes) with nuclear cataract of grade five (LOCS III) before and after cataract surgery (phacoemulsification). Their visual acuity before the cataract surgery was between 6/12 and 6/18. The postoperative period was from 2 to 3 months. None of the subjects had any significant eye disease apart from cataract. The mfERG responses were grouped into six concentric rings for analysis. Both the amplitudes and the latencies of N1 and P1 of first-order responses were used for analysis. RESULTS: N1 amplitude only from ring 1 increased significantly after cataract surgery. P1 amplitude from ring 1 and ring 2 also increased significantly after cataract surgery. The latencies of neither N1 nor P1 from all rings changed significantly. CONCLUSIONS: Nuclear cataract could affect the topography of mfERG, so clinicians should be aware of the effects of cataract when interpreting mfERG responses in cataract patients.

Aged↗