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PubMed1999

Na,K-ATPase in lens epithelia from patients with senile cataracts.

Sodium-potassium-adenosine triphosphatase (Na,K-ATPase) has long been recognized for its role in regulating electrolyte concentrations in the lens, within which the electrolyte balance is vital to lens transparency. In this study, we compared the abundance of the alpha-subunit of Na,K-ATPase in lens epithelia of patients with senile cataracts, in order to examine the role of this enzyme in various types of lens opacity. Human lens epithelia were collected from 27 patients with senile cataracts who had undergone phacoemulsification. The type and the severity of lens opacity were graded and scored according to the Lens Opacities Classification System II. The mean age of the patients was 67.5 years (range, 46-80 yr). Abundance of the Na,K-ATPase alpha-subunit peptide in the lens epithelium was quantified by means of Western immunoblotting. Immunoblotting revealed that the amount of Na,K-ATPase alpha-subunit tended to decrease with increased cataract severity. In hypermature cataracts, the Na,K-ATPase alpha-subunit was barely detectable. The amount of alpha-subunit of Na,K-ATPase was inversely correlated with the overall severity of cataract (r = -0.64, p = 0.002). However, the inverse correlation was significant only in the cortical region (p = 0.027). As the cortex is located adjacent to the lens epithelium, it is directly affected by the loss of function of Na,K-ATPase in the epithelium. Such loss could result in water accumulation, vesicles, water clefts, Morgagnian globule formation, and Morgagnian cataract.

Aged↗
PubMed1999

Intravitreal injection of TGFbeta induces cataract in rats.

PURPOSE: In a previous study, it was determined that TGFbeta induces cataractous changes in the rat lens in vitro. The purpose of the present study was to determine whether the introduction of biologically active TGFbeta into the vitreous stimulates cataractous changes in the rat lens in situ. METHODS: TGFbeta was injected into the vitreous of the left eye of anesthetized adult male Wistar rats. The right eye received sterile vehicle as a control. Three to four months after injection, animals were killed, and lenses were enucleated and examined for cataractous changes. RESULTS: All lenses from control eyes remained transparent and maintained normal cellular architecture throughout. In contrast, lenses from TGFbeta-injected eyes displayed cloudiness in the cortex. In some lenses, distinct opacities were also apparent at the equator and extending some distance toward the anterior and posterior poles. Histologically, the opacities corresponded to subcapsular plaques containing aberrant cells and accumulations of extracellular matrix. In addition, cortical fibers in the anterior and posterior of all lenses displayed variable degrees of swelling, and many retained their nuclei. In some regions, the fiber cells appeared to have degenerated to form large homogeneous areas. The cellular architecture of the equator of these lenses was also disrupted and, in the most severe case, no bow zone was apparent with nucleated cells extending to the posterior pole. CONCLUSION: The introduction of active TGFbeta into the vitreous induced lenses to undergo cataractous changes. In addition to the TGFbeta-induced changes in the epithelium that were reported previously, cataractous changes observed in this study also involved the lens fiber cells and resembled changes observed in human posterior subcapsular and cortical cataracts.

Animals↗
PubMed2000

A new locus for autosomal dominant congenital cataracts maps to chromosome 3.

PURPOSE: To map a gene for cataracts in a family with congenital nuclear and sutural cataracts and to examine candidate genes in the linked region. METHODS: A large family with autosomal dominant congenital nuclear and sutural cataracts was identified and characterized. A genome-wide screen was conducted with a set of markers spaced at 10- to 15-cM intervals, and linkage was assessed using standard LOD score analysis. RESULT: Fifteen (15) affected individuals were identified. This form of congenital cataracts maps to a 12-cM region on chromosome 3q21.2-q22.3 between markers D3S3674 and D3S3612, with a maximum multipoint LOD score of 6.94 at D3S1273. The crystallin gene, CRYGS, was excluded as a candidate gene for this locus. CONCLUSIONS: There are now more than 12 different genetic loci that cause congenital cataracts. The most recent locus to be identified is on chromosome 3q21.2-q22.3, in a family with congenital nuclear and sutural cataracts.

Adult↗
PubMed2000

Decimalization of The Oxford Clinical Cataract Classification and Grading System.

BACKGROUND: A secure methodology for the classification of cataracts into subtypes and for their separate quantification forms a fundamental underpinning of cataract research. The Oxford Clinical Cataract Classification and Grading System provides for this need across a wide range of cataract subtypes. Consideration of the advantages of finer scale intervals in terms of both increased precision and increased sensitivity to change (responsiveness) has stimulated the development of a decimal version of the Oxford system. AIM: To describe rules for the decimalization of the Oxford system and to document the performance following decimalization. METHOD: Theoretical considerations followed by iterative piloting were used to define a set of rules for the decimalization of grading for 10 cataract features. The performance of the decimal version was then formally tested by means of inter- and intra-observer comparisons of repeated measurements. 217 paired observations were pooled to produce a statement relevant to the 'multi-user' environment typical of many clinical research programmes. RESULTS: Repeatability indices were good to excellent for most features. The use of finer scale intervals improved the system's ability to detect change (reduced 95% tolerance limits for change) by a factor of around 2 for most features. CONCLUSION: The finer scale intervals provided by decimalization of the Oxford system have produced substantial improvements in reliability as evidenced by high levels of repeatability and scale sensitivity. These improvements provide practical advantages in clinical cataract research.

Cataract↗
PubMed2000

DeltaFosB-induced cataract.

PURPOSE: The objective of this study was to investigate a possible relationship between posterior subcapsular cataract (PSC) formation and expression of the transcription factor DeltaFosB. METHODS: Western blot analysis was performed on bitransgenic NSE-tTA, TetOp-DeltaFosB, and single-transgenic NSE-tTA control mice to determine the pattern of DeltaFosB expression within the eye. Light and scanning electron microscopy and biochemical analyses were also performed. RESULTS: In mice expressing DeltaFosB, cataract developed that initially appeared to be posterior subcapsular and gradually matured to involve the entire lens. The enlarged posterior ends of developing secondary fibers curved away from the visual axis to form an elevated opaque posterior plaque. As a result, posterior suture formation did not occur. At a later time, the attenuated posterior capsule overlying the plaque ruptured and the lens nucleus subluxated into the vitreous. Retinal damage was also observed but only from postnatal day 65, a time when extensive lens degeneration had already occurred. DeltaFosB expression was observed well before the detection of morphologic change in both the lens and the retina. Within the lens, DeltaFosB expression was found in both the epithelium and fibers. The development of cataracts was a direct consequence of DeltaFosB expression and was not due to the disruption of an endogenous gene by transgene integration since cataracts could be prevented by silencing expression of DeltaFosB by feeding bitransgenic animals doxycycline (Dox). Moreover, cataracts were observed in bitransgenic mice derived from two independent TetOp-DeltaFosB founder lines but not in single NSE-tTA transgenic controls. Cataractogenesis was not a consequence of abnormal development, because mice conceived and raised on Dox to prevent expression of DeltaFosB also were subject to formation of PSC when expression of DeltaFosB was turned on in adult animals by removing Dox. Examination of biochemical parameters indicated that the earliest change observed was the disruption of calcium homeostasis with a significant increase in Ca(2+) influx, followed by a gradual but marked decrease in protein content. Significant changes in certain metabolic parameters and protein composition were also observed. CONCLUSIONS: The DeltaFosB-induced cataract in which the major morphologic early event was the disruption of normal posterior fiber formation, may be a good model for PSC. By identifying DeltaFosB-regulated target genes, it should be possible to achieve a better understanding of the molecular mechanisms through which PSC is formed.

Animals↗
PubMed2000

[Ambulatory cataract surgery].

UNLABELLED: The purpose of this study is to show the result of outpatient cataract surgery and its differences or advantages with inpatient cataract surgery. PATIENTS AND METHODS: The retrospective study concern 722 consecutives patients collected from June 1995 till May 1997; 388 underwent outpatient cataract surgery and 384 underwent inpatient cataract surgery. RESULTS: There were non significant difference between the two groups in type of cataract surgery. Immediate postoperative complications and final visual acuity did not show any significant difference in both groups. CONCLUSION: This analysis shows the great advantages of this simple surgical procedure such an increase in cataract operation leading to a decrease of patients in waiting list.

Adolescent↗
PubMed2000

Molecular genetics of cataract.

Studies on hereditary congenital cataracts have led to the identification of genes involved in formation of these cataracts. Knowledge of the structure and function of a particular gene and the effect of disease-associated mutations on its function are providing insights into the mechanisms of cataract. Identification of the disease gene requires both the relevant clinical data as well as genetic data on the entire pedigree in which the disease is found to occur. Genes for hereditary cataract have been mapped by genetic linkage analysis, in which one examines the inheritance pattern of DNA markers throughout the genome in all individuals of the pedigree, and compares those with the inheritance of the disease. Cosegregation of a set of markers with disease implies that the disease gene is present at the same chromosomal location as those markers. The genes so far identified for hereditary cataracts in both humans and animal models encode structural lens proteins, gap junction proteins, membrane proteins and regulatory proteins involved in lens development. Understanding of the mechanisms of hereditary cataract may also help us understand the manner in which environmental and nutritional factors act on the lens to promote opacification.

Animals↗
PubMed2001

Natural therapies for ocular disorders, part two: cataracts and glaucoma.

Pathophysiological mechanisms of cataract formation include deficient glutathione levels contributing to a faulty antioxidant defense system within the lens of the eye. Nutrients to increase glutathione levels and activity include lipoic acid, vitamins E and C, and selenium. Cataract patients also tend to be deficient in vitamin A and the carotenes, lutein and zeaxanthin. The B vitamin riboflavin appears to play an essential role as a precursor to flavin adenine dinucleotide (FAD), a co-factor for glutathione reductase activity. Other nutrients and botanicals, which may benefit cataract patients or help prevent cataracts, include pantethine, folic acid, melatonin, and bilberry. Diabetic cataracts are caused by an elevation of polyols within the lens of the eye catalyzed by the enzyme aldose reductase. Flavonoids, particularly quercetin and its derivatives, are potent inhibitors of aldose reductase. Glaucoma is characterized by increased intraocular pressure (IOP) in some but not all cases. Some patients with glaucoma have normal IOP but poor circulation, resulting in damage to the optic nerve. Faulty glycosaminoglycan (GAG) synthesis or breakdown in the trabecular meshwork associated with aqueous outflow has also been implicated. Similar to patients with cataracts, those with glaucoma typically have compromised antioxidant defense systems as well. Nutrients that can impact GAGs such as vitamin C and glucosamine sulfate may hold promise for glaucoma treatment. Vitamin C in high doses has been found to lower IOP via its osmotic effect. Other nutrients holding some potential benefit for glaucoma include lipoic acid, vitamin B12, magnesium, and melatonin. Botanicals may offer some therapeutic potential. Ginkgo biloba increases circulation to the optic nerve; forskolin (an extract from Coleus forskohlii) has been used successfully as a topical agent to lower IOP; and intramuscular injections of Salvia miltiorrhiza have shown benefit in improving visual acuity and peripheral vision in people with glaucoma.

Cataract↗
PubMed2001

Macular pigment optical density before and after cataract extraction.

PURPOSE: Psychophysical methods of measuring macular pigment (MP) use comparisons of short- and midwave light in the fovea and parafovea to derive optical density estimates. This light must pass through the crystalline lens before absorption by the MPs can occur. The effect of lens absorption on these measures has not been adequately determined. The present study assesses the influence of lens absorption on MP measurements by comparing MP optical density (MPOD) measured before and after cataract extraction. METHODS: MPOD was measured using flicker photometry in free view at 458 nm with a 1 degrees stimulus. Twenty-nine eyes from 24 patients with cataracts sufficiently severe to require cataract extraction were evaluated. RESULTS: In the entire group of 24 patients, the mean (+/-SD) age measured 68.7 +/- 9.5 years, and the mean MPOD measured 0.19 +/- 0.11. For all 29 eyes measured, MPOD averaged 0.206 +/- 0.13 before and 0.18 +/- 0.12 after cataract extraction. MPOD measurements at the two time points (mean 8.1 +/- 4.7 weeks after surgery) were highly correlated (r = +0.58), suggesting that a cataractous lens does not influence the MP measurement technique. CONCLUSIONS: Psychophysical techniques can be used to obtain reliable measurements of MP in elderly subjects, even in those with cataracts. Moreover, differences in retinal illuminance due to varying opaqueness of the crystalline lens do not seem to have a measurable influence on MPOD.

Aged↗
PubMed2001

Multilamellar bodies as potential scattering particles in human age-related nuclear cataracts.

PURPOSE: To characterize within human age-related nuclear cataracts rare spherical objects covered by multiple membranes, termed multilamellar bodies (MLBs). METHODS: Adult human normal, transparent lenses were obtained from eye bank donors and age-related nuclear cataracts were obtained immediately after extracapsular extraction. Each sample was Vibratome sectioned fresh into 200 microm thick sections that were fixed and embedded for light or electron microscopy. Confocal images were recorded from sections stained with the lipid soluble dye, DiI. RESULTS: Light micrograph montages of the equatorial plane containing the fetal and embryonic nuclei were examined. Rare, but distinct, circular 1-3 microm diameter objects were observed consistently in the cataracts. These objects did not appear to be components of the complex intercellular interfaces. Serial sections indicated that the objects were spherical, or contained a spherical component. For about 20,000 fiber cell cross-sections in each lens, the frequency of MLBs was 10 times higher in cataracts than in the normal lens nuclei. Although extensive searching with the electron microscope was necessary, the size, circular profile and multiple layers of thin (5 nm) membranes easily identified the MLBs. Interiors of the MLBs displayed variable textures. Confocal images indicated that the coverings were enriched in lipid compared to the adjacent plasma membranes. The calculated density of the MLBs in the cataractous nuclei was about 3800/mm3, which represents a volume fraction of 0.00003. CONCLUSIONS: Because the MLBs are large compared to the wavelength of light, display interiors with variable staining textures and have lipid-rich coverings, they appear to be ideal candidates for large scattering particles that may contribute to the forward light scattering in nuclear cataracts.

Aged↗
PubMed2001

[Cataract surgery with posterior chamber lens implantation in Senegalese children less than 15 year-old].

PURPOSE: To assess short and medium term outcomes of cataract surgery with intraocular lens implantation in Senegalese children less than fifteen years. METHODS: From 1992 to 1997, 50 eyes of 40 children between the age of 5 months and 14 years, suffering from cataract were operated. Some of them were seen untill 2000. Twenty-seven cataracts were congenital, 19 were traumatic, 2 were from corticosteroid side effects, 1 after uveitis, and 1 had no determined cause. Thirty-one had manual extracapsular surgery and 19 ultrasound cataract surgery. They all have a standard single-piece PMMA intraocular lens of 21 to 22 diopters, 12.0-12.5mm long, under the ciliaris silcus (34 cases) or in the capsular bag (16). The results were noted in the first week, at one month, at 3 months, and after. RESULTS: Exudative reactions were frequent in the anterior chamber: 20% of the eyes had such reactions during the operation, especially when a manual extracapsular extraction was performed, and 34% soon after operation. The reactions were generally revealed with one month of survey. Corticosteroids used before and after surgery reduced inflammation disorders but seemed to speed up the onset of secondary cataract. Posterior capsule opacification was observed in the first week after surgery. It increased from 45% at 3 months to 74% at 1 year and 100% after 3 years. Intraocular cristal lens implants are well tolerated with limited complications. Fifty-seven percent of the operated eyes we observed after 3 years had 30/60 or better visual acuity. CONCLUSION: Despite fairly frequent inflammation and secondary cataract, posterior chamber lens implantation in children is well tolerated. This suggest that, as in adults, intraocular lens implant would be the best treatment for aphakia.

Cataract Extraction↗
PubMed2002

Decreased expression of ribosomal proteins in human age-related cataract.

PURPOSE: To identify lens epithelial genes with altered expression levels in age-related human cataract. METHODS: Epithelia from age-related cataracts and from normal lenses were microdissected and RNA was extracted. RNAs were compared for gene expression differences by RT-PCR differential display. Transcripts exhibiting altered levels of gene expression were cloned and identified by sequencing. The expression levels of identified clones were confirmed by semiquantitative RT-PCR with three separately isolated RNA preparations. Specific primers were designed and used to examine the mRNA levels of other genes important in protein synthesis. RESULTS: Numerous transcripts exhibited altered levels of gene expression. One transcript exhibiting a decreased level of expression in cataract compared with normal lenses was identified as encoding ribosomal protein L21. Three additional ribosomal proteins, L15, L13a, and L7a, also exhibited decreased expression in cataract compared with normal human lenses. By contrast, the levels of elongation factor (EF)-1alpha1 and eucaryotic initiation factor (eIF)-4E remained unchanged. CONCLUSIONS: The results provide evidence that human age-related cataract is associated with decreased expression of L21 and other ribosomal proteins. The results suggest that modulation of protein synthesis and/or other functions mediated by ribosomal proteins is associated with age-related cataract.

Aged↗
PubMed2002

Expression and effect of basic fibroblast growth factor on human cataract lens epithelial cells.

OBJECTIVE: To detect the expression of basic fibroblast growth factor (bFGF) in human ocular tissues, and to assess the effect of bFGF on the proliferation of human cataract lens epithelial cells (LECs) and its correlation with age. METHODS: Enucleated eyes were subjected to immunostaining for bFGF protein. Human cataract LECs were cultured in vitro, and treated with bFGF for 48 hr. Proliferation was estimated by the positive area ratio of proliferating cell nuclear antigen (PCNA) in immunohistochemistry. RESULTS: bFGF protein was found in various human ocular tissues. bFGF stimulated human cataract LEC proliferation, and there was an age-related decrease in responsiveness of human cataract LECs to bFGF (P < 0.05). CONCLUSION: bFGF might play an important role in the proliferation of residual human cataract LECs after cataract surgery.

Adolescent↗
PubMed2002

Cataract surgery in uveitis.

PURPOSE: To study the visual outcome of cataract surgery in eyes with uveitis. METHODS: A retrospective analysis of patients with uveitis operated for cataract. RESULTS: 106 eyes of 89 patients with uveitis were operated for cataract. In 62.3% eyes (66/106), post-operative follow-up was at least 6 months. There was significant improvement (P < 0.001) in visual acuity after cataract surgery. Provided the uveitis was well controlled for three months pre-operatively, additional pre-operative anti-inflammatory medications did not significantly affect (P = 0.842) post-operative inflammation. Patients who received extracapsular cataract extraction (ECCE) or phacoemulsification with posterior chamber IOL (PCIOL) obtained better visual acuity at 6 weeks (P = 0.009 and P = 0.032 respectively) than those with only ECCE without IOL. In 37 eyes vision did not improve due to persistent uveitis (23.9%, 16/67), cystoid macular oedeme (20.9%, 14/67), and posterior capsule opacification (14.9%, 10/67). CONCLUSION: Cataract extraction and PCIOL implantation is safe in eyes with uveitis. Additional preoperative medications may not alleviate post-operative inflammation if uveitis is well controlled for at least three months before surgery.

Adolescent↗
PubMed1999

[Free radicals on cataracts induced by sodium selenite studied by ESR and LPO].

We made a electron spin resonance (ESR) study on rat cataracts induced by Na2SeO3. A signal was detected at about g = 2.0026, and the content of electron spins (CES) in lens of rat administrated Na2SeO3 for a short time is higher than that of control significantly. At the late stage of cataracts, the content of CES was lower than normal level. The results of kinetics analysis showed that the CES grow up with the administration of Na2SeO3 and decays in index-law after administration. The results suggested that free radical scavengers or antioxidants should be useful for preventing cataracts at initial stage of the oxidation damage to lens, but they could aggravate cataracts at late stage of cataracts. This can explain the controversy about the curative effect of antioxidant to cataracts.

Animals↗
PubMed2002

Altered patterns of phosphorylation in cultured mouse lenses during development of buthionine sulfoximine cataracts.

Buthionine sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis, induces oxidative cataracts following multiple injections into mice at 1 week of age. Cultures of lenses with (35)S-methionine have previously demonstrated altered patterns of protein biosynthesis that precede and accompany these cataracts. To obtain parallel information about changes in protein phosphorylation during cataract development, lenses from BSO-treated or control mouse pups were cultured for 3 hr at 37 degrees C with (32)P(i), homogenized in phosphate buffer, and resolved by centrifugation into water-soluble (WS) and water-insoluble (WI) fractions. These were characterized by 2D-gel electrophoresis, Coomassie blue staining, phosphorimaging, immunoblotting, and tandem mass spectrometry. Heaviest labelling was in the WI fraction. The labelled 2D-gel spots included: (1) a series of phosphorylated filensins at 95 kDa; (2) a major radioactive spot at 45-50 kDa, slightly anodic to actin and the beaded filament protein, phakinin (CP 49); (3) a phosphorylated betaB1-crystallin, considerably anodic to parent betaB1; (4) an acidic cluster of labelled alphaA-crystallins, phosphorylated in part at serine-148, and (5) a labelled trace alpha crystallin, slightly anodic to alphaB-crystallin. The results confirm previously reported phosphorylations of actin, phakinin, alphaA- and alphaB-crystallin, demonstrate previously unrecognized phosphorylations of filensin and betaB1-crystallin, and provide unequivocal evidence for phosphorylation of alphaA-crystallin at serine-148. The earliest changes in phosphorylation detected after BSO treatment were increased labelling of alphaA- and alphaB-crystallin during cataract stages 1-3, coupled with a general decrease in protein labelling. In stage 5 cataracts, phosphorylated alpha crystallins persisted as the dominant labelled species. However, the major modifications of alphaA-crystallin in advanced BSO cataracts were unlabelled and partially degraded, in contrast to phosphorylated alphaA. It is therefore proposed that phosphorylation of alphaA-crystallin may confer resistance to proteolytic degradation.

Animals↗
PubMed1999

[Diathermic high-frequency capsulorhexis in cataract surgery].

PURPOSE: To evaluate the efficiency of diathermic high-frequency capsulorhexis in cataract surgery. METHODS: After injection of viscoelastic material into the anterior chamber, a continuous circular capsulotomy (CCC) was performed using a diathermic high-frequency capsulorhexis machine in 34 eyes of 30 cataract patients during extracapsular cataract extraction (ECCE) combined with intraocular lens (IOL) implantation. RESULTS: Successfully CCC was made in 31 eyes. A small peripheral radial capsular tear was detected in 3 eyes. No postoperative corneal edema and other complications were found in all eyes. The postoperative corrected visual acuity > or = 0.5 was accounted for 91.2%. CONCLUSION: Diathermic high-frequency capsulorhexis is a simple, safe and effective method for ECCE (or Phacoemulsification) combined with IOL implantation. It is especially indicated for those eyes with hypermature cataract, traumatic cataract and children with congenital cataract.

Aged↗
PubMed2002

[A study of human lens epithelial cells by light and electron microscopy and by immunohistochemistry in different types of cataracts].

PURPOSE: To evaluate the characteristics of cataract changes in lens epithelial cells (LECs), in different types of human cataract. MATERIAL AND METHODS: Anterior capsules for the study were obtained from patients with different types of cataracts during extracapsular cataract extraction, or phacoemulsification using continuous curvilinear capsulorhexis. LECs attached to the anterior capsules were analyzed for morphological changes by light and electron microscopy, and for cellular characteristics by immunohistochemistry. The reactivity to cytokeratins 5,6,8,17 and 19 (arker for epithelial cells) and to vimentin (arker for mesenchymal cells) was determined. RESULTS: The consecutive degenerative changes were observed in most of the cells: multilayered cells, nuclei of abnormal diameters and shapes, vacuolation of nuclei and cytoplasm. LECs were immunohistochemically positive for cytokeratin and vimentin, or only for vimentin in all types of cataract. Some of LECs showed morphological and immunohistochemical characteristics of mesenchymal cells. CONCLUSIONS: Lens epithelial cells show similar degenerative changes in different types of cataract and may have the ability to transdifferentiate into mesenchymal cells.

Adult↗