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PubMed1997

The HNK-1 epitope in the pseudophakic and aphakic eye and secondary cataract.

PURPOSE: To search for changes in the presence and distribution of the cell-adhesion-related HNK-1 carbohydrate epitope after cataract extraction. METHODS: Twenty-five pseudophakic and two aphakic human autopsy eyes and, for comparison, one anterior subcapsular cataract obtained at surgery were studied with monoclonal antibodies (MAbs) HNK-1 and NC-1 to the HNK-1 epitope using the avidin-biotinylated peroxidase complex method. RESULTS: MAbs to the HNK-1 epitope constantly immunolabelled the inner connective tissue layer of the ciliary body in all pseudophakic and aphakic eyes studied. The distribution of the immunoreaction was similar to that reported for normal eyes. They also labelled the extracellular matrix in each of 18 plaques of secondary cataract on the posterior capsule, in each of 13 plaques at the rim of the capsular bag, and in the anterior subcapsular cataract. Bladder cells in each of 16 Soemmering's rings remained unlabelled. CONCLUSION: The distribution of the HNK-1 epitope in the ciliary body does not appreciably change after cataract extraction, although the accommodative demand of the eye is altered. Its presence in an anterior subcapsular cataract suggests that the epitope may be locally produced by lens epithelial cells also in secondary cataract. The epitope is associated with cell adhesion and migration, both of which may play a role in the pathogenesis of secondary cataract.

Aged↗
PubMed1993

Autofluorescence in cataractous human lens and its relationship to light scatter.

The autofluorescence profile of the lens was measured from 84 eyes of 84 patients with cortical, nuclear, posterior subcapsular, or mixed lens opacities. Measurements were performed with a fluorometer in the blue-green autofluorescence range (495 nm/520 nm). The mean maximum autofluorescence value differed in every cataract group statistically significantly from that of the age matched controls (p < or = 0.0058). The highest autofluorescence values were measured in nuclear and mixed cataract groups (p < 0.0001) with high and narrow autofluorescence profile. In cortical cataracts the curve was low and flattened and the mean maximum autofluorescence value was lower than in the control eyes (p < 0.0001). The maximum autofluorescence was related to lens coloration as well as to visual acuity only in nuclear cataract. The regression between maximum autofluorescence and light scatter was statistically significant only in the nuclear cataract group (p = 0.0004). Since the autofluorescence profiles differed not only in height but also in width between the cataract groups, various width/maximum autofluorescence ratios were measured. In nuclear and mixed cataract groups the ratio 75% width/maximum autofluorescence was statistically significantly lower than in other groups (p < 0.0001). In cortical cataracts the ratio (50% width - 75% width)/maximum autofluorescence was statistically significantly higher than in other groups (p < 0.0001).

Adult↗
PubMed1994

The relationship between cataract and climatic droplet keratopathy in Mongolia.

This study evaluated the association between cataract, the commonest single blinding disorder worldwide, and climatic droplet keratopathy which was taken as an indicator of high exposure to ultraviolet sunlight. A sample of 4344 persons from rural Mongolia (1991-92) provided 8634 eyes for analysis of the relationship between cataract and climatic droplet keratopathy. Right and left eyes were combined (paired into matched sets), and analysed using a random-effects regression model. The results indicated an inverse association between cataract and climatic droplet keratopathy in person aged 55 years or older, whereby eyes with more advanced climatic droplet keratopathy had lower prevalence of cataract (age-adjusted odds ratio 0.53, p = 0.047). In the younger group of persons aged 40-54 years, the reverse was found, whereby cataract prevalence was higher in eyes that have climatic droplet keratopathy (age-adjusted odds ratio 13.19, p = 0.046). However, only a small proportion (4%) of all the cataracts occurred in this younger age stratum where the prevalence of cataract was 0.5%, compared to prevalence of 17% in eyes of persons aged 55 years or older. These findings cast further doubts upon the current thesis that lifetime exposure to high levels of ultraviolet sunlight is a major cause of cataract in developing countries.

Adult↗
PubMed1989

Allopurinol use and the risk of cataract formation.

Several reports have suggested an association between chronic allopurinol ingestion and cortical and subcapsular cataract formation. To examine this possibility we identified 51 allopurinol users and compared their lenses with those of 76 patients who did not use allopurinol. The existence of lens opacities and the level of visual acuity were assessed by review of medical records or by prospective ophthalmic examinations; in both phases of the study the examiners were blinded as to the patient's use or non-use of allopurinol. Three different outcomes were considered: formation of any cataract, formation of a posterior subcapsular cataract, and formation of a cataract contributing to a corrected visual acuity of 20/30 or worse. The risk ratio for the formation of any cataract was 1.3 (95% confidence interval: 0.8, 2.0), the risk ratio for the formation of a posterior subcapsular cataract was 0.9 (0.3, 2.0), and the risk ratio for the formation of a cataract contributing to a loss of visual acuity was 1.3 (0.6, 2.9). None of these risk ratios was changed appreciably after controlling for age, sex, hypertension, or diabetes. Thus, after a mean of 6.9 years of allopurinol use, we found no evidence to confirm that allopurinol users were at higher risk of acquiring cataracts.

Allopurinol↗
PubMed2002

Enhanced expression of transglutaminase 2 in anterior polar cataracts and its induction by TGF-beta in vitro.

BACKGROUND/AIMS: Transglutaminase activity has long been implicated in the cataract formation. However, the precise mechanism of how it is produced and involved in this process remains unclear. Here the authors sought to examine whether transglutaminase 2 (TGase 2) is expressed in lens epithelial cells from patients with anterior polar cataracts, to determine whether TGase 2 expression is induced by transforming growth factor (TGF-beta) in cultured lens epithelial cells, and to determine whether TGase 2 participates in the crosslinking of fibronectin in lens epithelial cells in vitro. METHODS: Lens epithelial cells from anterior polar cataracts, nuclear cataracts, and non-cataractous clear lenses were examined for the expression of TGase 2 using reverse transcription-polymerase chain reaction, western blot analysis, and immunohistochemical analysis. The modulation of extracellular TGase 2 activity by TGF-beta was measured by the formation of fibronectin polymers and the incorporation of fluorescein cadaverine into extracellular matrix proteins. The effect of TGase 2 overexpression was analysed by immunofluorescence staining and western blot analysis of human lens epithelial (HLE) B-3 cells transiently transfected with TGase 2 gene. RESULTS: The expression of TGase 2 mRNA and its protein was markedly enhanced in lens epithelial cells from patients with anterior polar cataracts. Treatment of HLE B-3 cells with TGF-beta caused an increase in TGase 2 protein, its extracellular activity, and the crosslinking of fibronectin. Transient transfection of HLE B-3 cells with the TGase 2 gene led to the increased production of fibronectin monomers and polymers. CONCLUSIONS: This study shows that TGase 2 is overexpressed in lens epithelial cells from anterior polar cataracts and that TGF-beta may be a causative factor in the induction of TGase 2. The enhanced expression of TGase 2 might cause the accumulation and crosslinking of the extracellular matrix proteins and might play a part in anterior polar cataract development.

Aged↗
PubMed2002

Childbearing and risk of cataract in young women: an epidemiological study in central India.

BACKGROUND/AIMS: Observations in central India, over a period of more than a decade, suggested that the frequency of sight restoring cataract surgery was substantially higher in women of childbearing age compared to men of the same age. Formal surveys in the subcontinent of India have confirmed a higher prevalence of cataract in women. The present study was conducted to explore possible effects of childbearing and associated adverse factors on cataract risk. METHODS: A case-control study design was used. Cases were mothers aged 35-45 with bilateral "senile" cataract. Controls were mothers of the same age but with clear lenses, attending the hospital services with other, mostly minor, complaints. RESULTS: A significant association was found between childbearing and risk of sight impairing cataract in mothers. Having more than three babies doubled the risk (adjusted odds ratio 2.0, p=0.012), and the risk increased by an estimated 20% for each additional birth. The birth effect was independent of age, socioeconomic status (occupation and income level), body mass index, and multiple episodes of severe dehydration, all regarded as putative risk factors for cataract. CONCLUSIONS: Having more than three babies may substantially increase the risk of sight impairing cataract in mothers of childbearing age in central India. The findings open new research challenges to identify cataract risk factors to which mothers may be exposed during pregnancy and childbirth, particularly under poor socioeconomic conditions.

Adult↗
PubMed2003

Comparing the efficacy and safety of phacoemulsification in white mature and other types of senile cataracts.

AIM: To compare the intraoperative difficulty and postoperative outcome in patients who have white mature cataract in one eye and other types of senile cataract in the other eye undergoing clear corneal phacoemulsification and foldable intraocular lens implantation. METHODS: 82 patients who had white mature cataract in one eye, posterior subcapsular, cortical, nuclear, or mixed type cataract in the other eye were enrolled in this prospective study. Postoperative outcomes, intraoperative difficulties related to capsulorhexis, and phacoemulsification were analysed between the two groups of eyes. Postoperative examinations were done at 1 day, 1 week, 1 and 3 months. RESULTS: Postoperative visual acuity, central corneal thickness, intraocular pressure, and rate of posterior capsule rupture were not significantly different between the two group of eyes (p>0.05). Mean effective phaco time, frequency of postoperative corneal oedema and posterior capsular plaque were found to be significantly higher in the mature cataract group (p<0.05). CONCLUSIONS: A one stage, 5 mm continuous capsulorhexis was achieved using trypan blue and generous amounts of retentive viscoelastic agent in eyes with white mature cataract. Intraoperative difficulties and postoperative outcome of clear corneal incision phacoemulsification surgery and foldable intraocular lens implantation were similar in white mature and other types of senile cataract. Topical anaesthesia in phacoemulsification of eyes with white mature cataract is safe and well tolerated.

Aged↗
PubMed1992

Serum antioxidant vitamins and risk of cataract.

OBJECTIVE: To investigate serum concentrations of alpha tocopherol, beta carotene, retinol, and selenium for their prediction of end stage cataract. DESIGN: A case-control study, nested within a cohort study, based on the linkage of records of subjects aged 40-83 from a health survey with those from the national Finnish hospital discharge register. SUBJECTS: 47 patients admitted to ophthalmological wards for senile cataract over 15 years and two controls per patient individually matched for sex, age, and municipality. MAIN OUTCOME MEASURE: Concentration of serum micronutrients, development of cataract according to whether operation was performed. RESULTS: Low serum concentrations of antioxidant vitamins predicted the development of senile cataract, the odds ratio between the lowest third and the two higher thirds of the distribution of serum concentrations of alpha tocopherol and beta carotene being 1.9 (95% confidence interval 0.9 to 4.1) and 1.7 (0.8 to 3.8), respectively. Patients with both alpha tocopherol and beta carotene concentrations in the lowest third had an odds ratio of 2.6 (1.0 to 6.8) of cataract compared with subjects in the top two thirds. The associations were strengthened by adjustment for potential confounding factors such as occupation, smoking, blood pressure, serum cholesterol concentration, body mass index, and diabetes. No association was found between the serum concentrations of selenium, retinol, and retinol binding protein and the risk of cataract. CONCLUSIONS: Low serum concentrations of the antioxidant vitamins alpha tocopherol and beta carotene are risk factors for end stage senile cataract. Controlled trials of the role of antioxidant vitamins in cataract prevention are therefore warranted.

Adult↗
PubMed2006

A new locus for autosomal dominant posterior polar cataract in Moroccan Jews maps to chromosome 14q22-23.

BACKGROUND: Posterior polar cataract is a clinically distinctive opacity located at the back of the lens. It is commonly acquired in age related cataract, and may infrequently occur in pedigrees with congenital cataract. To date, five loci for autosomal dominant congenital posterior polar cataract have been identified. These include two genes, CRYAB and PITX3, on chromosomes 11q and 10q respectively, and three loci with as yet unknown genes on chromosomes 1p, 16q and 20p. PURPOSE: To find the chromosomal location of a gene causing autosomal dominant congenital posterior polar cataract in three Moroccan Jewish families. METHODS: A whole genome scan was performed using microsatellite markers spaced at approximately 10 cM intervals. For fine mapping, five additional microsatellite markers were genotyped. Two-point lod scores were calculated using MLINK software, from the LINKAGE program package. After linkage was established, several positional candidate genes were assessed by PCR based DNA sequencing. RESULTS: The new cataract locus was mapped to an 11.3 cM interval between D14S980 and D14S1069 on chromosome 14q22-23. A maximum two point lod score of 5.19 at theta = 0 was obtained with the markersD14S274. The positional and functional candidate genes SIX1, SIX4, SIX6, OTX2, and ARHJ were excluded as the cause of cataract in these families. CONCLUSION: An as yet unidentified gene associated with posterior polar cataract maps to the long arm of chromosome 14q22-23.

Adult↗
PubMed1990

Nutritional factors in cataract.

Age-related cataract is a condition characterized by multiple mechanisms and multiple risk factors. The mechanisms that bring about a loss in transparency include oxidation, osmotic stress, and chemical adduct formation. Risk factors for cataract include diabetes, radiation (ultraviolet B, x-ray), certain pharmaceutical substances, certain nutritional states, and possibly acute episodes of dehydration. Interaction occurs between and among mechanistic factors and risk factors. Thus nutrition must be considered as one part of a tapestry of intertwined events and responses. Certain experimental models for nutritional cataract have been useful for study of the cataractogenic process but are probably not important factors in the human disease. Little current evidence supports significant roles in human senile cataract for imbalances of tryptophan or other amino acids, deficiencies of calcium or selenium, or excessive intake of selenium. Overconsumption of galactose is likely to be hazardous only in subjects with genetic inability to metabolize this sugar. Vitamins with antioxidant potential (riboflavin, vitamin E, vitamin C, carotenoids) deserve further research scrutiny to ascertain their significance in cataract etiology. Excessive caloric intake needs to receive added emphasis as a factor contributing to cataract. Diabetes increases the likelihood of cataract three- to four-fold. Obesity, defined as more than 20% overweight, is considered a major risk factor for non-insulin-dependent, or type II, diabetes (69, 73). Weight control can be recommended as a prudent, safe, economic, and effective means of lowering risk probability for diabetes and the associated complication of cataract.

Aging↗
PubMed2005

A point mutation in the iron-responsive element of the L-ferritin in a family with hereditary hyperferritinemia cataract syndrome.

BACKGROUND: Hereditary hyperferritinemia cataract syndrome is an autosomal dominant condition that is characterized by a high serum ferritin level and bilateral early-onset cataracts in the absence of iron overload. The genetic abnormality is identified as a mutation in the 5' regulatory region of the L-ferritin messenger RNA known as the iron-responsive element (IRE). The IRE controls ferritin synthesis in response to cytoplasmic iron pools by interacting with regulatory proteins called iron responsive proteins. Mutations in the IRE decrease its affinity for iron responsive proteins, leading to the constitutive synthesis of L-ferritin which results in hyperferritinemia and the intracellular accumulation of ferritin in the lens and eventual cataract formation. PATIENTS AND METHODS: A 22-year-old woman who was being investigated for hyperferritinemia was diagnosed with hereditary hyperferritinemia cataract syndrome after an extensive workup, including genetic testing for hemochromatosis and a liver biopsy to rule out iron overload. She developed anemia with phlebotomy treatments and subsequently developed symptomatic cataracts. The pedigree of her family affected with cataracts was consistent with an autosomal dominant transmission pattern. DNA was extracted from peripheral leukocytes of eight family members, four of whom were affected by cataracts. Polymerase chain reaction amplification of the 5' region of the L-ferritin gene was performed and a heterozygous point mutation (G32T) was identified in the bulge region of the IRE. CONCLUSION: The combination of early-onset cataracts and an elevated ferritin level should suggest this genetic syndrome.

Adult↗
PubMed2006

Protective effect of aspirin against dexamethasone-induced cataract in cultured rat lens.

PURPOSE: To investigate the effect of aspirin on dexamethasone-induced cataract formation in cultured rat lenses. METHODS: One hundred and forty-eight lenses were divided into 3 groups and cultured in vitro: control (DMEM), cataract (DMEM + 10 microM dexamethasone), aspirin (DMEM + 10 muM dexamethasone + 2 mM aspirin). Following incubation, the transparency of the lenses was evaluated daily using a dissecting microscope. Twelve lenses from each group were homogenized and the activities of enzymes (catalase, superoxide dismutase and lactate dehydrogenase) from supernatants were measured after 1, 3, 5 and 7 days of incubation, respectively. The ultrastructure of lenses from the control and cataract groups was observed on the completion of 7-day incubation. RESULTS: Opacity was induced by dexamethasone in the nuclear region of the rat lenses. Lenses in the control group exhibited mist-like opacity and lenses in the cataract group showed dense nuclear opacity, whereas lenses in the aspirin-treated group only had a visible demarcation between nuclear and cortical regions at day 7. The activities of catalase, superoxide dismutase and lactate dehydrogenase in the cataract group decreased in a time-dependent manner. There was no significant loss of enzyme activities in either the control or the aspirin group throughout the incubation period. An orderly arrangement of fiber cells was noted, and the cell membrane, cell junction and organelles were normal in the control group. However, in the cataract group the arrangement of fiber cells was untidy and the lenses contained abnormal-appearing cells. The group exhibited swollen mitochondria, a large number of vacuoles and expanded extracellular lacunae. CONCLUSIONS: Dexamethasone induces nuclear cataract in the organ-cultured rat lens by chemically modifying proteins, including enzymes. The enzymes, including those that normally eliminate radial oxygen species, could be especially vulnerable. Aspirin significantly inhibits dexamethasone-induced cataract formation by inhibiting inactivation of those enzymes.

Animals↗
PubMed1989

Photographic and spectroscopic correlations of human cataracts.

Intracapsular cataracts obtained within 3 h after surgical extraction were photographed with the CCRG technique and immediately subjected to fluorescence spectroscopy followed by 31P- and 13C-nuclear magnetic resonance (NMR) spectroscopy. Fluorescence spectroscopy demonstrates an excellent correlation between nontryptophan fluorescence intensities and lens color. An interesting correlation was also observed between the degree of light scatter as determined by the 290-nm excitation peak for intrinsic lens tryptophan fluorescence and the CCRG (photographic) appearance of these cataractous lenses. Based on 100 cataracts analyzed, there is a strong correlation between this kind of light scattering measurement and the type and degree of lens opacification. A similar correlation is evident with the 31P-NMR organophosphate profiles in the lenses in which the sugar phosphate levels are elevated only in diabetic patients with cataracts ('diabetic cataracts'). Aside from fluorescence and 31P-NMR spectroscopy, selected lenses were also incubated with 5.5 nM 13C-glucose as soon as they were obtained, and the foregoing spectroscopy was performed, followed by 13C-NMR analyses to detect and monitor for sorbitol accumulation in young versus old normal lenses and in diabetic cataracts. These studies clearly demonstrate a direct correlation between nontryptophan-fluorescent chromophore levels, light scattering (determined by tryptophan excitation peaks), lens age and cataract type. In addition, the organophosphate profiles clearly delineate the diabetic cataracts, and the 13C-NMR spectra correlate well with the age-related decrease in aldose reductase activity.

Aged↗
PubMed1990

Reproducibility studies with the Zeiss SLC system and animal cataract models.

Scheimpflug photography has become the basic method for documentation of lens transparency changes in clinical and experimental ophthalmology, due to its high reproducibility. In animal cataract studies, the reproducibility is strongly influenced by the handling characteristics of the camera used, due to limited cooperation of the animal. The reproducibility of the Zeiss SLC system, which offers a direct quality control of the image on the video screen, was tested with 2 animal cataract models, the ultraviolet B (UVB)-induced cataract and the true diabetic cataract in the Brown-Norway rat. 10 rats each of the 2 cataract models and of an untreated control group were photographed in a random order on 3 occasions on the same day by the same photographer. Quality control and densitometry were performed by the same system operator, the measurement window was positioned standardly, coincident with the optical axis of the eye. Statistical comparison was carried out in the capsular layer, that is the area of initial cataract development in both models, and in the cortical layer, into which the diabetic cataract progresses during its later stages of development. The nuclear layer was also evaluated, but has no direct relation to one of the models employed. The results clearly indicate that the reproducibility is predominantly influenced by the homogeneity or inhomogeneity of the cataract model employed. The system operator and the photographer provided that they are well trained, have minor influence on the reproducibility of the Zeiss SLC system.

Animals↗
PubMed1987

Evaluation of cataract-related risk factors using detailed classification systems and multivariate statistical methods.

The well-known different morphological features observed in so-called senile cataract are probably symptoms of various pathogenetic mechanisms in the lens. In order to identify a relationship between type of cataract and special risk factors, a cataract classification system using Scheimpflug photography has been developed. Data of 288 cataract patients (case histories and blood chemistries) have been grouped according to differences in cataract morphology. The multivariate analyses showed the following five variables to be important and to contribute independently to the differentiation of cataract types: cholelithiasis, allergy, heart insufficiency, pneumonia, and age. A case-control study without consideration of cataract morphology showed the following variables to be important and to associate independently with the risk of developing cataracts: age, allergy, diabetes, hypotension, hypertension, use of analgesics, and coronary disease.

Age Factors↗
PubMed2003

Localization of cortical cataract in subjects of diverse races and latitude.

PURPOSE: To compare the characteristics of early cortical cataract localization in three groups in cataract epidemiologic surveys performed in Reykjavík, Melbourne, and Singapore. METHODS: Individuals who had right eyes with an area of cortical opacity less than 20% of the pupil when dilated 7 mm or more were selected as subjects. This included 197 subjects from the Reykjavík Eye Study, 231 from the Vitamin E, Cataract, and Age-Related Maculopathy (VECAT) study in Melbourne, and 92 from the Singapore-Japan Cooperative Cataract Study, all showing early-stage cataract in pupils dilated to 7 mm or more. Scheimpflug and retroilluminated photographs were used to locate opacities. Localization of cortical cataract was determined by dividing the retroillumination image into seven concentric circles with diameters of 1 through 7 mm, and eight sections of 45 degrees radial octants. The positive rate of opacification was then calculated for each quadrant. RESULTS: The highest positive rate of opacification was observed in the lower nasal quadrant in all groups. The relative risk of the prevalence of cortical opacity in the lower nasal oblique hemisphere to the upper temporal oblique hemisphere was the highest in the Singaporean subjects followed by those of Melbourne and then of Reykjavík. CONCLUSIONS: The prevalence of cortical cataract was higher in the lower nasal quadrant than in the other quadrants for all subjects of diverse race in three climatically different locations. This higher prevalence was most pronounced in subjects living at low latitude. These results support the view that solar UV exposure is a possible risk factor for development of human cortical cataract.

Aged↗
PubMed2004

Protein-bound kynurenine decreases with the progression of age-related nuclear cataract.

PURPOSE: Posttranslational modification by UV filters is a key event in human lenses that appears to be largely responsible for normal age-dependent yellowing. It has been proposed that subsequent reactions of these covalently bound UV filters may also be involved in the genesis of age-related nuclear cataract. To examine this hypothesis, the levels of kynurenine-lysine and kynurenine-histidine were measured in both normal and cataractous human lenses. METHODS: Proteins isolated from the nuclei of normal lenses and lenses with and types I to IV nuclear cataract were hydrolyzed in 6 M HCl, and the levels of kynurenine-lysine and kynurenine-histidine were determined by HPLC. RESULTS: The content of kynurenine-lysine and kynurenine-histidine decreased substantially with the progression of age-related nuclear cataract. On average, levels of both kynurenine adducts were four times lower in advanced cataract (type IV) than in normal lenses. Simple autoxidation of the derivatives did not appear to be responsible for this decrease, because incubation in the presence of oxygen or H(2)O(2) did not affect adduct stability. CONCLUSIONS: Although protein-bound kynurenine accumulates over time in normal lenses, the levels attached to the proteins decrease significantly with the progression of age-related nuclear cataract. This finding suggests that in cataract there is a breakdown of the protein-bound adducts. Such further reactions of bound UV filters may contribute to the etiology of age-related nuclear cataract.

Aged↗
PubMed2004

Coordinate signaling by Src and p38 kinases in the induction of cortical cataracts.

PURPOSE: The goals of this study were to determine whether MAP kinase signaling pathways play a role in the formation of lens cataracts and to examine the potential signaling relationship between Src and MAP kinases in signaling the induction of lens opacities. METHODS: Embryonic day (E)10 chick lenses were cultured in Medium 199 containing 10% fetal bovine serum. The activation state of Src kinases and the MAP kinases extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the lens epithelium was determined over a time course from 10 minutes to 10 days in culture by immunoblot analysis. Src kinase activation was suppressed by exposure to the Src family kinase-specific inhibitor PP1. To examine the role of specific MAP kinases in the development of lens opacities, lenses were grown for 10 days in the presence or absence of inhibitors of ERK (U0126), JNK (SP600125), and p38 (SB203580). Lenses were observed and photographed daily, and the degree of opacification was quantified by using image-analysis software. RESULTS: Within a short time after placing embryonic lenses in culture conditions that induce the formation of cataracts, there occurred a great increase in the activation state of the MAP kinase ERK. Activation of ERK was both rapid and transient. No activation of the MAP kinase JNK was observed in the cataract cultures beyond that which occurred in normal lens epithelium, even though JNK activation is often linked to the cellular response to stress. In contrast, although p38 activation was barely detected in the normal embryonic lens, this stress-activated protein kinase exhibited a robust activation in cataract cultures that was sustained throughout the culture period. Studies conducted to map the cataract signaling pathways indicate that the p38 MAP kinase functions upstream of the Src kinase. To analyze the potential role of ERK, JNK, and p38 in cataract induction, lenses were cultured in the presence of specific MAP kinase inhibitors. Although the inhibitors of ERK and JNK did not interfere with the formation of cataract, p38 inhibitors blocked the development of lens opacities with an efficacy similar to that of the Src kinase inhibitor PP1. CONCLUSIONS: Activation of both Src and p38 kinases lead to the induction of cataract.

Animals↗