?A crystallin may protect against geographic atrophy-meta-analysis of cataract vs. cataract surgery for geographic atrophy and experimental studies.
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ABSTRACT: Background
Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.Methods/principal findings
We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84-7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR=3.23, 95% CI: 0.63-16.47). Further experiments were performed to analyze how the ?A-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that the?A-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO(3) in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in ?A-crystallin knockout mice compared to wild-type mice.Conclusions
Therefore, ?A-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.
SUBMITTER: Zhou P
PROVIDER: S-EPMC3423426 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
αA crystallin may protect against geographic atrophy-meta-analysis of cataract vs. cataract surgery for geographic atrophy and experimental studies.
Zhou Peng P Ye Hong-Fei HF Jiang Yong-Xiang YX Yang Jin J Zhu Xiang-Jia XJ Sun Xing-Huai XH Luo Yi Y Dou Guo-Rui GR Wang Yu-Sheng YS Lu Yi Y
PloS one 20120820 8
<h4>Background</h4>Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.<h4>Methods/principal findings</h4>We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary ...[more]
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| S-EPMC6441871 | biostudies-literature
Project description:ImportanceApproximately 2 million cataract operations are performed annually in the US, and patterns of cataract surgery delivery are changing to meet the increasing demand. Therefore, a comparative analysis of visual acuity outcomes after immediate sequential bilateral cataract surgery (ISBCS) vs delayed sequential bilateral cataract surgery (DSBCS) is important for informing future best practices.ObjectiveTo compare refractive outcomes of patients who underwent ISBCS, short-interval (1-14 days between operations) DSBCS (DSBCS-14), and long-interval (15-90 days) DSBCS (DSBCS-90) procedures.Design, setting, and participantsThis retrospective cohort study used population-based data from the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry. A total of 1 824 196 IRIS Registry participants with bilateral visual acuity measurements who underwent bilateral cataract surgery were assessed.ExposuresParticipants were divided into 3 groups (DSBCS-90, DSBCS-14, and ISBCS groups) based on the timing of the second eye surgery. Univariable and multivariable linear regression models were used to analyze the refractive outcomes of the first and second surgery eye.Main outcomes and measuresMean postoperative uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) after cataract surgery.ResultsThis study analyzed data from 1 824 196 patients undergoing bilateral cataract surgery (mean [SD] age for those <87 years, 70.03 [7.77]; 684 916 [37.5%] male). Compared with the DSBCS-90 group, after age, self-reported race, insurance status, history of age-related macular degeneration, diabetic retinopathy, and glaucoma were controlled for, the UCVA of the first surgical eye was higher by 0.41 (95% CI, 0.36-0.45; P < .001) letters, and the BCVA was higher by 0.89 (95% CI, 0.86-0.92; P < .001) letters in the DSBCS-14 group, whereas in the ISBCS group, the UCVA was lower by 2.79 (95% CI, -2.95 to -2.63; P < .001) letters and the BCVA by 1.64 (95% CI, -1.74 to -1.53; P < .001) letters. Similarly, compared with the DSBCS-90 group for the second eye, in the DSBCS-14 group, the UCVA was higher by 0.79 (95% CI, 0.74-0.83; P < .001) letters and the BCVA by 0.48 (95% CI, 0.45-0.51; P < .001) letters, whereas in the ISBCS group, the UCVA was lower by -1.67 (95% CI, -1.83 to -1.51; P < .001) letters and the BCVA by -1.88 (95% CI, -1.98 to -1.78; P < .001) letters.Conclusions and relevanceThe results of this cohort study of patients in the IRIS Registry suggest that compared with DSBCS-14 or DSBCS-90, ISBCS is associated with worse visual outcomes, which may or may not be clinically relevant, depending on patients' additional risk factors. Nonrandom surgery group assignment, confounding factors, and large sample size could account for the small but statistically significant differences noted. Further studies are warranted to determine whether these factors should be considered clinically relevant when counseling patients before cataract surgery.
| S-EPMC8251655 | biostudies-literature
Project description:ImportancePrevious studies using data from the 1980s found relatively little geographic variation in cataract surgery rates across the United States. We do not know whether similar patterns hold true today, nor do we know the patient- and community-level factors that might explain any recent geographic variations in the rate and timing of cataract surgery.ObjectiveTo assess the extent of geographic variation in patient age at initial cataract surgery and the age-standardized cataract surgery rate in a large group of insured US patients with cataracts.Design, setting, and participantsRetrospective cross-sectional study of 1 050 815 beneficiaries older than 40 years of age with cataracts who were enrolled in a nationwide managed-care network during the period from 2001 to 2011. The data analysis was started in 2014 and refined in 2015.Main outcomes and measuresMedian age at initial cataract extraction, age-standardized cataract surgery rate, and time from initial diagnosis to first surgery for patients with cataracts were compared among 306 US communities. Multivariable regression modeling generated hazard ratios (HRs) with 95% CIs identifying factors associated with patients' likelihood of undergoing cataract surgery.ResultsA total of 243 104 patients with cataracts (23.1%) underwent 1 or more surgical procedures (55.1% were female patients). Communities with the youngest and oldest patients at initial surgery differed in age by nearly 20 years (59.9-60.1 years in Lansing, Michigan, and Aurora, Illinois, vs 77.0-79.6 years in Marquette, Michigan; Rochester, New York; and Binghamton, New York). The highest age-standardized cataract surgery rate (37.3% in Lake Charles, Louisiana) was 5-fold higher than the lowest (7.5% in Honolulu, Hawaii). The median time from initial cataract diagnosis to date of first surgery ranged from 17 days (Victoria, Texas) to 367 days (Yakima, Washington). Compared with white patients, black patients had a 15% decreased hazard of surgery (HR, 0.85 [95% CI, 0.83-0.87]), while Latino patients (HR, 1.08 [95% CI, 1.05-1.10]) and Asian patients (HR, 1.09 [95% CI, 1.05-1.12]) had an increased hazard. For every 1° higher latitude, the hazard of surgery decreased by 1% (HR, 0.99 [95% CI, 0.98-0.99]). For every additional optometrist per 100 000 enrollees in a community, the hazard of surgery increased 0.1% (HR, 1.001 [95% CI, 1.001-1.001]).Conclusions and relevanceIn recent years, patient age at first cataract surgery and the age-standardized surgery rate have varied considerably among some US communities. Future research should explore the extent to which such variations may affect patient outcomes.
| S-EPMC5767078 | biostudies-literature
Project description:Connexin mutant mice develop cataracts containing calcium precipitates. To test whether pathologic mineralization is a general mechanism contributing to the disease, we characterized the lenses from a nonconnexin mutant mouse cataract model. By cosegregation of the phenotype with a satellite marker and genomic sequencing, we identified the mutant as a 5-bp duplication in the γC-crystallin gene (Crygcdup). Homozygous mice developed severe cataracts early, and heterozygous animals developed small cataracts later in life. Immunoblotting studies showed that the mutant lenses contained decreased levels of crystallins, connexin46, and connexin50 but increased levels of resident proteins of the nucleus, endoplasmic reticulum, and mitochondria. The reductions in fiber cell connexins were associated with a scarcity of gap junction punctae as detected by immunofluorescence and significant reductions in gap junction-mediated coupling between fiber cells in Crygcdup lenses. Particles that stained with the calcium deposit dye, Alizarin red, were abundant in the insoluble fraction from homozygous lenses but nearly absent in wild-type and heterozygous lens preparations. Whole-mount homozygous lenses were stained with Alizarin red in the cataract region. Mineralized material with a regional distribution similar to the cataract was detected in homozygous lenses (but not wild-type lenses) by micro-computed tomography. Attenuated total internal reflection Fourier-transform infrared microspectroscopy identified the mineral as apatite. These results are consistent with previous findings that loss of lens fiber cell gap junctional coupling leads to the formation of calcium precipitates. They also support the hypothesis that pathologic mineralization contributes to the formation of cataracts of different etiologies.
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Project description:ImportanceThe iStent Trabecular Micro-Bypass (Glaukos Corporation) is a minimally invasive glaucoma implant used in conjunction with cataract surgery to lower intraocular pressure.ObjectiveTo determine whether implantation of the iStent concurrent with cataract surgery is associated with reduced use of ocular antihypertensive medications in a US health care claims database.Design, setting, and participantsRetrospective, observational longitudinal cohort study of individuals enrolled in a US managed care network who underwent iStent implantation with cataract surgery (iStent/CEIOL) from 2012 to 2016 (n = 1509 bilateral and n = 1462 unilateral surgery). A control group of individuals who underwent bilateral cataract surgery only (CEIOL) were matched 1:1 to patients undergoing bilateral iStent/CEIOL on baseline demographic and clinical factors. Data were analyzed between November 1, 2017, and January 31, 2018.Main outcomes and measuresThe number of topical ocular antihypertensive agents used postoperatively by patients undergoing iStent/CEIOL compared with baseline and with matched CEIOL control individuals, and hazard ratios with 95% confidence intervals for sustained reduced use of at least 1 topical ocular antihypertensive agent postoperatively.ResultsOf the 2971 eligible enrollees, mean age at first surgery was 74.3 years, and 1659 (55.8%) were women. Patients undergoing iStent/CEIOL had diagnoses that included primary open-angle glaucoma (n = 2329; 78.4%), narrow angles (n = 381; 12.8%), and secondary glaucomas (n = 261; 8.8%). At baseline, 1223 (41.2%) were receiving no topical glaucoma agents; 876 (29.5%), 437 (14.7%), and 435 (14.6%) were receiving 1, 2, or at least 3 agents, respectively. Although only 678 persons (22.8%) completed at least 2 years of postoperative follow-up, the proportion of patients receiving no drops increased postoperatively (64.7%, 20-24 months, P < .001, χ2). Patients receiving at least 1 topical agent at baseline had mean reduction of 1.01 and 0.61 medications used at 20 to 24 months with bilateral or unilateral surgery, respectively (both P < .001, paired t). Sustained reduction in glaucoma medication use was more likely in patients receiving at least 3 vs 1 medication at baseline (hazard ratio, 1.68; 95% CI, 1.36-2.09). Compared with matched control individuals undergoing CEIOL, patients undergoing bilateral iStent/CEIOL had a greater mean reduction in drops used (0.99 vs 0.49; postoperative month 20-24; P < .001; paired t) and a higher proportion receiving no drops postoperatively (73.5% vs 55.3%, postoperative month 20-24; P < .001; χ2).Conclusions and relevanceImplantation of the iStent trabecular micro-bypass stent concurrent with cataract surgery was associated with moderately reduced use of topical ocular antihypertensive medication. Reduction in the use of glaucoma medications may lessen the burden of medication adverse effects and promote better adherence.
| S-EPMC6439782 | biostudies-literature
Project description:Creatine kinase (CK) is an energy storage enzyme that plays an important role in energy metabolism. CK/phosphocreatine functions as an energy buffer and links ATP production sites with ATP utilization sites. Several key mutations in the ?A-crystallin (cryaa) and ?B-crystallin (cryab) genes have been linked with autosomal-dominant, hereditary human cataracts. The cryaa-R49C mutation was identified in a four-generation Caucasian family. We previously identified an increase in the quantity of CK complexed with ?-crystallin in the lenses of knock-in mice expressing the cryaa-R49C mutation using proteomic analyses. Increased levels of CK in postnatal cataractous lenses may indicate increased ATP requirements during early cataract development. To gain a further understanding of the relationship between CK and ?-crystallin, we investigated whether ?-crystallin interacts with and forms complexes with CK, in vitro. Isothermal titration calorimetry (ITC) showed that each CK dimer bound to 28 ?-crystallin subunits, with a Kd of 3.3 × 10-7 M, and that the interaction between ?-crystallin and CK was endothermic, thermodynamically favorable, and entropy-driven. High-salt concentrations did not affect the interaction between CK and ?-crystallin, suggesting that the interaction between CK and ?-crystallin is primarily hydrophobic. Gel permeation chromatography (GPC) detected water-soluble ?-crystallin and CK complexes, as determined by increased light scattering after complex formation. In addition, CK and ?-crystallin formed partially-water-insoluble, high-molecular-mass complexes. Enzyme-linked immunosorbent assay (ELISA)-based enzymatic activity analyses of lens homogenates showed a 17-fold increase in CK activity in the postnatal lenses of cryaa-R49C knock-in mice. These studies indicate that the interaction between ?-crystallin and CK is functionally important and that increased CK levels may be necessary to meet the increased ATP demands of ATP-dependent functions in cataractous lenses.
| S-EPMC7052508 | biostudies-literature
Project description:BackgroundA substitution mutation in human ?A-crystallin (?AG98R) is associated with autosomal dominant cataract. The recombinant mutant ?AG98R protein exhibits altered structure, substrate-dependent chaperone activity, impaired oligomer stability and aggregation on prolonged incubation at 37 °C. Our previous studies have shown that ?A-crystallin-derived mini-chaperone (DFVIFLDVKHFSPEDLTVK) functions like a molecular chaperone by suppressing the aggregation of denaturing proteins. The present study was undertaken to determine the effect of ?A-crystallin-derived mini-chaperone on the stability and chaperone activity of ?AG98R-crystallin.Methodology/principal findingsRecombinant ?AG98R was incubated in presence and absence of mini-chaperone and analyzed by chromatographic and spectrometric methods. Transmission electron microscope was used to examine the effect of mini-chaperone on the aggregation propensity of mutant protein. Mini-chaperone containing photoactive benzoylphenylalanine was used to confirm the interaction of mini-chaperone with ?AG98R. The rescuing of chaperone activity in mutant?-crystallin (?AG98R) by mini-chaperone was confirmed by chaperone assays. We found that the addition of the mini-chaperone during incubation of ?AG98R protected the mutant crystallin from forming larger aggregates that precipitate with time. The mini-chaperone-stabilized ?AG98R displayed chaperone activity comparable to that of wild-type ?A-crystallin. The complexes formed between mini-?A-?AG98R complex and ADH were more stable than the complexes formed between ?AG98R and ADH. Western-blotting and mass spectrometry confirmed the binding of mini-chaperone to mutant crystallin.Conclusion/significanceThese results demonstrate that mini-chaperone stabilizes the mutant ?A-crystallin and modulates the chaperone activity of ?AG98R. These findings aid in our understanding of how to design peptide chaperones that can be used to stabilize mutant ?A-crystallins and preserve the chaperone function.
| S-EPMC3435407 | biostudies-literature
Project description:PurposeThe aim of this study was to evaluate corneal endothelial cell density and morphology, central corneal thickness, and best visual acuity using ultrasound (US) phacoemulsification or nanosecond laser technique.SettingDepartment of ophthalmology, Nabeul, Tunisia.DesignProspective cohort study.MethodsThis study included eyes with nuclear cataracts with a density grade of 1, 2, 3, or 4 according to LOCS III, divided into two groups; group 1 had conventional US, and group 2 had nanosecond laser. The endothelial cell density (ECD), coefficient of variation (CoV) in cell size, percentage of hexagonal cells, central corneal thickness (CCT) and best visual acuity (VA) were evaluated during 24 months.ResultsSeventy-four eyes had uneventful surgery, 40 in group 1, 34 in group 2. Three procedures in group 2 required conversion to standard phacoemulsification. The mean ECD decreased from 2616.4 ± 194.6 cells/mm2 in group 1 preoperatively to 2088.4 ± 229.9 after 2 years. In group 2, it decreased from 2611.8 ± 186.5 cells/mm2 to 2276.4 ± 163.8 after 2 years. The change was statistically significant in both groups. The decline of the mean ECD in group 2 was significantly less important than in group 1 (p = <10-2). The mean percentage of hexagonal cells was 45.18 ± 4.9 preoperatively and 43.5% ± 6.6 after 2 years in group 1. In group 2, it remained almost stable with 45.6 ± 5.1 and 45.4% ± 6.6 preoperatively and after 2 years, respectively. Preoperatively, the mean CoV was 0.39 ± 0.037 in group 1 and 0.38 ± 0.04 in group 2. After 2 years, it was 0.38 ± 0.04 and 0.37 ± 0.038 in group 1 and group 2, respectively. The changes of the mean CoV and the mean percentage of hexagonal cells were significant in both groups, but the difference between the groups was significant only during the six first months postoperatively. In preoperative, the mean corneal central thickness was 509.7 ± 19.5 in group 1 and 510.3 ± 20.4 in group 2. In both groups, the mean corneal thickness increased on D1 postoperatively to 550.9 in group 1, and 528.2 in group 2. The mean corneal thickness decreased more rapidly after 1 week in group 2, to find the initial values. Visual acuity improved from 0.76 Log Mar ± 0.5 at enrolment to 0.45 Log Mar ± 0.2, and 0.033 Log Mar ± 0.086 in group 1 at 1 day post-operative and after 24 months, respectively and from 0.58 Log Mar ± 0.28 to 0.2 Log Mar ± 0.09 and 0.035 Log Mar ± 0.083, respectively in group 2. There was no significant difference in VA at each follow-up between groups except for day 1.ConclusionOur study showed lower corneal tissue trauma, and lower endothelial cell loss in the laser cataract surgery compared to phacoemulsification.Clinical trial registration: (https://classic.clinicaltrials.gov/ct2/show/NCT05886283), identifier NCT05886283.
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Project description:PURPOSE: To compare the outcomes of phacoemulsification with either a 2.5-mm clear corneal incision and a foldable intraocular lens (IOL) or a 5-mm sclerocorneal tunnel incision and a rigid polymethyl methacrylate (PMMA) IOL. METHODS: In a prospective, randomised clinical trial of phacoemulsification cataract surgery, 1200 patients received either a foldable hydrophilic acrylic IOL through a 2.5-mm corneal incision or an inexpensive rigid PMMA IOL via a 5-mm sclerocorneal tunnel. Intra- and post-operative data and visual acuity at discharge, 6 weeks, and 1 year follow-up were analysed. RESULTS: At 1 year after surgery, 996 (83.0%) patients were followed up with an uncorrected visual acuity of 6/18 or better in 90.3% of the foldable and 94.3% in the rigid IOL group (risk ratio (RR) 0.96, 95% confidence intervals (CI) 0.92-0.99). Poor outcome (best-corrected acuity 6/60 or worse) occurred in 1.0% and 0.4%, respectively (RR 4.28, 95% CI 0.48-38.18). The surgical cost of consumables and overall surgical time were similar in both groups; however, the cost of the foldable IOL was eight times higher than the PMMA IOL. Posterior capsule opacification was more common in the rigid IOL group at 12 months (36.1% vs 23.3%); however, this did not affect post-operative vision. CONCLUSION: In the hands of experienced cataract surgeons, phacoemulsification with implantation of a foldable or a rigid IOL gives excellent results. Using an inexpensive rigid PMMA IOL will make phacoemulsification more affordable for poor patients in low- and middle-income countries.
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