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1.
Ophthalmic Res ; 67(1): 221-231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38493781

RESUMO

INTRODUCTION: The aim of this study was to investigate the efficacy of new monofocal intraocular lens (IOL) in comparison with conventional monofocal IOL in patients undergoing combined cataract and vitrectomy surgery for epiretinal membrane (ERM). METHODS: This prospective non-randomized comparative study included 65 eyes of 65 patients who underwent combined cataract and vitrectomy for ERM with implantation of advanced monofocal IOL (Eyhance ICB00, 33 patients) and standard monofocal IOL (Tecnis ZCB00, 32 patients). Monocular visual acuities were measured 6 months post-operatively, including corrected and uncorrected distance visual acuity (CDVA, UCDVA), uncorrected intermediate visual acuity (UCIVA), and uncorrected near visual acuity (UCNVA). Furthermore, contrast sensitivity and metamorphopsia were measured. RESULTS: There was no significant difference between two groups regarding operation time, post-operative CDVA, UCDVA, UCNVA, and spherical equivalent (p > 0.05). Monocular UCIVA was significantly higher in the Eyhance IOL group than in the Tecnis IOL group (p = 0.005). The photopic and mesopic contrast sensitivities were comparable between each group for any spatial frequency (p > 0.05). The correlation coefficients from correlations between retinal wrinkling ratio and M score did not differ significantly between groups (p = 0.877), and the degree of metamorphopsia was not significantly related to the type of IOL (p = 0.969). CONCLUSIONS: In combined cataract and vitrectomy for ERM, Eyhance IOL provided significant better visual performance at intermediate distance than standard monofocal IOL without compromising operation time, distance vision, contrast sensitivity, and evaluating metamorphopsia. Eyhance IOL can be a useful option for both surgeons and patients.


Assuntos
Catarata , Membrana Epirretiniana , Implante de Lente Intraocular , Lentes Intraoculares , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Feminino , Masculino , Acuidade Visual/fisiologia , Estudos Prospectivos , Membrana Epirretiniana/cirurgia , Membrana Epirretiniana/fisiopatologia , Membrana Epirretiniana/diagnóstico , Idoso , Pessoa de Meia-Idade , Catarata/fisiopatologia , Catarata/complicações , Implante de Lente Intraocular/métodos , Sensibilidades de Contraste/fisiologia , Desenho de Prótese , Seguimentos , Resultado do Tratamento , Facoemulsificação/métodos
2.
J Biol Chem ; 299(8): 104935, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37331601

RESUMO

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.


Assuntos
Catarata , Cristalinas , Minerais , Animais , Camundongos , Cálcio/metabolismo , Catarata/genética , Catarata/fisiopatologia , Conexinas/genética , Conexinas/metabolismo , Cristalinas/genética , Cristalinas/metabolismo , Cristalino/patologia , Minerais/metabolismo , Microtomografia por Raio-X , Modelos Animais de Doenças
3.
Invest Ophthalmol Vis Sci ; 63(2): 22, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35147660

RESUMO

Purpose: To investigate the impact of the size and location of waterclefts (WC), which are one of several cataract subtypes, on visual function by optical simulation analysis. Methods: An optical simulation software (CODE V) was used to develop a schematic eye model and several sizes of WC central and peripheral types that were located below the anterior and posterior subcapsules of the crystalline lens, and analyses of refraction, higher-order aberrations (HOA), and the modulation transfer function (MTF) were performed. Results: An increase in the WC size increased the refraction and HOA and decreased the MTF. The impact of the WC below the posterior subcapsule on the visual function was more enhanced than that below the anterior subcapsule. Large WC demonstrated a remarkable hyperopic shift in refractive power as well as an increase in HOA. The MTF decreased slightly with increasing WC size at a spatial frequency of 20 cycles/mm, and it decreased remarkably at 60 cycles/mm. Conclusions: The impact on the visual function increased with increasing WC size. It was revealed that eyes with WC below the posterior subcapsule are more hyperopic than those with WC below the anterior subcapsule, and the former have a higher HOA and lower MTF than the latter.


Assuntos
Catarata/fisiopatologia , Simulação por Computador , Erros de Refração/fisiopatologia , Acuidade Visual/fisiologia , Idoso , Catarata/diagnóstico por imagem , Aberrações de Frente de Onda da Córnea/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Refração Ocular/fisiologia
5.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34751414

RESUMO

According to emerging evidence, long non­coding RNAs (lncRNAs) play critical roles in diabetes. The aim of the present study was to investigate the role and mechanism of X­inactive specific transcript (XIST) in cell proliferation, migration and apoptosis in diabetic cataracts (DC). SRA01/04 lens epithelial cells were treated with high glucose (HG). The levels of XIST, microRNA (miR)­34a and SMAD family member 2 (SMAD2) were examined via reverse transcription­quantitative PCR. MTT, Transwell, wound healing and TUNEL assays were performed to examine cell proliferation, invasion, migration and apoptosis, respectively. The interaction between miR­34a and XIST or SMAD2 was verified by luciferase reporter assay. It was found that the expression of XIST was increased and that of miR­34a was decreased in DC tissues and HG­treated SRA01/04 cells. XIST knockdown or miR­34a overexpression attenuated cell proliferation and migration, and induced apoptosis in HG­treated SRA01/04 cells. XIST targeted miR­34a and regulated DC progression through miR­34a. SMAD2 was identified as a target gene of miR­34a and was positively modulated by XIST. XIST knockdown inhibited cell proliferation and migration, and accelerated apoptosis in HG­stimulated SRA01/04 cells, and these effects were abrogated by SMAD2 overexpression. In conclusion, XIST promoted cell proliferation, migration and invasion, and inhibited apoptosis, through the miR­34a/SMAD2 axis in DC.


Assuntos
Catarata/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Smad2/metabolismo , Apoptose/genética , Catarata/metabolismo , Catarata/fisiopatologia , Movimento Celular/genética , Proliferação de Células/genética , China , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Células Epiteliais/metabolismo , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Proteína Smad2/genética
6.
Exp Eye Res ; 212: 108790, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648773

RESUMO

Age related nuclear (ARN) cataracts in humans take years to form and so experimental models have been developed to mimic the process in animals as a means of better understanding the etiology of nuclear cataracts in humans. A major limitation with these animal models is that many of the biochemical and physiological changes are not typical of that seen in human ARN cataract. In this review, we highlight the work of Frank Giblin and colleagues who established an in vivo animal model that replicates many of the changes observed in human ARN cataract. This model involves exposing aged guinea pigs to hyperbaric oxygen (HBO), which by causing the depletion of the antioxidant glutathione (GSH) specifically in the lens nucleus, produces oxidative changes to nuclear proteins, nuclear light scattering and a myopic shift in lens power that mimics the change that often precedes cataract development in humans. However, this model involves multiple HBO treatments per week, with sometimes up to a total of 100 treatments, spanning up to eight months, which is both costly and time consuming. To address these issues, Giblin developed an in vitro model that used rabbit lenses exposed to HBO for several hours which was subsequently shown to replicate many of the changes observed in human ARN cataract. These experiments suggest that HBO treatment of in vitro animal lenses may serve as a more economical and efficient model to study the development of cataract. Inspired by these experiments, we investigated whether exposure of young bovine lenses to HBO for 15 h could also serve as a suitable acute model of ARN cataract. We found that while this model is able to exhibit some of the biochemical and physiological changes associated with ARN cataract, the decrease in lens power we observed was more characteristic of the hyperopic shift in refraction associated with ageing. Future work will investigate whether HBO treatment to age the bovine lens in combination with an oxidative stressor such as UV light will induce refractive changes more closely associated with human ARN cataract. This will be important as developing an animal model that replicates the changes to lens biochemistry, physiology and optics observed in human ARN cataracts is urgently required to facilitate the identification and testing of anti-cataract therapies that are effective in humans.


Assuntos
Envelhecimento , Catarata/metabolismo , Oxigenoterapia Hiperbárica/métodos , Cristalino/química , Óptica e Fotônica , Animais , Catarata/fisiopatologia , Bovinos , Humanos , Cristalino/diagnóstico por imagem , Cristalino/fisiologia , Microscopia com Lâmpada de Fenda
7.
Exp Eye Res ; 212: 108777, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34597677

RESUMO

We have investigated how connexin 46 (Cx46) regulates lens stiffness by studying different Cx46 knockout (Cx46KO) mice. A modified muscle lever system was used to determine the lens stiffness of wild-type (WT) and Cx46KO mice at the C57BL/6J (B6) and the 129SvJae (129) strain backgrounds according to total lens displacement at the point of maximum force when fresh lenses were compressed with a maximum of 2 mN of force. In comparison to B6-WT controls, young and old B6-Cx46KO lenses showed 23% and 28% reductions in lens displacement, respectively. Comparing to 129-WT controls, old 129-Cx46KO lenses showed 50% reduction in the lens displacement while young 129-Cx46KO lenses displayed similar displacement. Old B6-Cx46KO and old 129-Cx46KO lenses showed almost identical lens displacement, 128 µm versus 127 µm. Morphological data revealed unique changes of peripheral fiber cell shapes in young B6-WT lenses but not in young B6-Cx46KO, 129-WT and 129-Cx46KO lenses. This work reveals Cx46 deletion increases the lens stiffness in both young and old mice at B6 strain background but only in old mice at 129 strain background which contains intermediate filament CP49 gene deletion. Cx46 impairment increases old mouse lens stiffness and may contribute to the development of presbyopia.


Assuntos
Envelhecimento/fisiologia , Catarata/fisiopatologia , Conexinas/genética , Cristalino/fisiopatologia , Animais , Catarata/metabolismo , Conexinas/metabolismo , Modelos Animais de Doenças , Elasticidade , Junções Comunicantes , Cristalino/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout
8.
Genes (Basel) ; 12(9)2021 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-34573385

RESUMO

This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the ABHD12 gene. A total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation [SD] ± 11.0; range from 17.5 to 53.9) at the most recent examination. The presence and onset of neurological, audiological and ophthalmic symptoms were variable, with no evident order of symptom appearance. The mean best-corrected visual acuity was 1.1 logMAR (SD ± 0.9; range from 0.1 to 2.8; equivalent to 20/250 Snellen) and showed a trend of progressive decline. Different types of cataract were observed in 13 out of 15 patients (87%), which also included congenital forms of cataract. Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%). From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity. Given the variable nature of PHARC, an early multidisciplinary assessment is recommended to assess disease severity.


Assuntos
Ataxia , Catarata , Olho/fisiopatologia , Monoacilglicerol Lipases/genética , Polineuropatias , Retinite Pigmentosa , Adolescente , Adulto , Ataxia/genética , Ataxia/patologia , Ataxia/fisiopatologia , Bélgica , Catarata/genética , Catarata/patologia , Catarata/fisiopatologia , Estudos de Coortes , Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Polineuropatias/genética , Polineuropatias/patologia , Polineuropatias/fisiopatologia , Pseudofacia/genética , Pseudofacia/patologia , Pseudofacia/fisiopatologia , Retinite Pigmentosa/genética , Retinite Pigmentosa/patologia , Retinite Pigmentosa/fisiopatologia , Estudos Retrospectivos , Reino Unido , Acuidade Visual/fisiologia , Adulto Jovem
9.
Sci Rep ; 11(1): 16141, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373485

RESUMO

To assess the repeatability and comparability of the Galilei G4 versus the Cassini topographer in post-refractive eyes and in normal eyes, including older patients representative of an initial cataract evaluation. Simulated keratometric (simK), total corneal and posterior corneal power and astigmatism were evaluated in both post-refractive and normal eyes. Repeatability was measured by calculating within-subject standard deviation (Sw), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Vector analyses and Bland-Altman plots were employed to assess agreement between devices. We studied 32 subjects with a history of refractive surgery and 32 subjects without a history of refractive surgery undergoing cataract surgery. The mean age was 55 ± 18.5 years and the age range was 21.5-91.5 years. In non-refractive and post-refractive eyes, the ICC was > 0.9 (P < 0.001) for all corneal powers and for simK and total corneal astigmatism for both analyzers. The ICC for posterior corneal astigmatism magnitude using the Galilei was 0.62 and 0.67 and for the Cassini 0.55 and 0.38 in normal and post-refractive eyes, respectively. In both post-refractive and normal eyes, the Galilei G4 and Cassini analyzers have high repeatability in simK, total, and posterior corneal power and low repeatability for posterior corneal astigmatism.


Assuntos
Astigmatismo/fisiopatologia , Catarata/fisiopatologia , Córnea/fisiopatologia , Topografia da Córnea/métodos , Procedimentos Cirúrgicos Refrativos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Astigmatismo/diagnóstico , Catarata/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Refração Ocular/fisiologia , Reprodutibilidade dos Testes , Testes Visuais/métodos , Adulto Jovem
10.
Sci Rep ; 11(1): 16107, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373536

RESUMO

This study investigates the etiology and clinical features of delayed vitreous prolapse after cataract surgery and evaluates the long-term surgical and visual outcomes. Consecutive patients with vitreous prolapse into the anterior chamber occurring ≥ 3 months after cataract surgery at two hospitals between December 2006 and June 2020 were retrospectively reviewed. The primary outcome was associated ophthalmological events that triggered delayed vitreous prolapse. Secondary outcomes included long-term visual and subjective symptom changes after treatment. Among 20 eyes (20 patients), all had visual symptoms, the most common being blurry vision (12 patients; 60%). Five (25%) were detected after YAG laser capsulotomy, three (15%) had a history of intraocular lens(IOL) implantation in sulcus due to intraoperative posterior capsular tears, three (15%) had prolapsed vitreous alongside dislocated IOLs, and three (15%) were aphakic after previous cataract surgeries. After surgical treatment, the mean corrected distance visual acuity improved from 20/50 to 20/31(P = 0.02) and the mean preoperative intraocular pressure (IOP) that was 26.4 mmHg decreased to 15.6 mmHg, remaining stable until the last follow-up. All reported symptoms were relieved. YAG laser capsulotomy or a history of defective posterior capsule from iatrogenic causes may trigger delayed vitreous prolapse. The long-term outcomes were favorable, particularly after posterior vitrectomy, with improved IOP control and symptom resolution.


Assuntos
Câmara Anterior/fisiopatologia , Catarata/fisiopatologia , Acuidade Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Câmara Anterior/cirurgia , Opacificação da Cápsula/cirurgia , Extração de Catarata/métodos , Feminino , Humanos , Pressão Intraocular/fisiologia , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular/métodos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Prolapso , Estudos Retrospectivos , Resultado do Tratamento , Transtornos da Visão/fisiopatologia , Transtornos da Visão/cirurgia , Vitrectomia/métodos
11.
J Biol Chem ; 297(3): 101089, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416235

RESUMO

Familial British dementia and familial Danish dementia are neurodegenerative disorders caused by mutations in the gene integral membrane protein 2B (ITM2b) encoding BRI2, which tunes excitatory synaptic transmission at both presynaptic and postsynaptic termini. In addition, BRI2 interacts with and modulates proteolytic processing of amyloid-ß precursor protein (APP), whose mutations cause familial forms of Alzheimer's disease (AD) (familial AD). To study the pathogenic mechanisms triggered by the Danish mutation, we generated rats carrying the Danish mutation in the rat Itm2b gene (Itm2bD rats). Given the BRI2/APP interaction and the widely accepted relevance of human amyloid ß (Aß), a proteolytic product of APP, to AD, Itm2bD rats were engineered to express two humanized App alleles and produce human Aß. Here, we studied young Itm2bD rats to investigate early pathogenic changes in these diseases. We found that periadolescent Itm2bD rats not only present subtle changes in human Aß levels along with decreased spontaneous glutamate release and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated responses but also had increased short-term synaptic facilitation in the hippocampal Schaeffer-collateral pathway. These alterations in excitatory interneuronal communication can impair learning and memory processes and were akin to those observed in adult mice producing rodent Aß and carrying either the Danish or British mutations in the mouse Itm2b gene. Collectively, the data show that the pathogenic Danish mutation alters the physiological function of BRI2 at glutamatergic synapses across species and early in life. Future studies will determine whether this phenomenon represents an early pathogenic event in human dementia.


Assuntos
Catarata/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Surdez/fisiopatologia , Demência/fisiopatologia , Proteínas de Membrana/genética , Transmissão Sináptica/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Catarata/metabolismo , Ataxia Cerebelar/metabolismo , Surdez/metabolismo , Demência/genética , Demência/metabolismo , Modelos Animais de Doenças , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , Feminino , Masculino , Proteínas de Membrana/metabolismo , Memória , Terminações Pré-Sinápticas/metabolismo , Ratos , Receptores de Glutamato/metabolismo , Sinapses/metabolismo
12.
Mol Vis ; 27: 384-395, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220184

RESUMO

Purpose: Ephrin (Eph) receptor A2 (EPHA2) polymorphism has been associated with age-related cataract (ARC) in different populations worldwide, but the mechanisms by which this polymorphism results in the development of ARC are unclear. Here, we chose four EPHA2 single nucleotide polymorphisms (SNPs; rs35903225, rs145592908, rs137853199, and rs116506614) and studied their function in human lens epithelial cells (LECs). Methods: The four EPHA2 mutants were overexpressed using lentiviral transduction in human LECs. Cells expressing wild-type (WT) and mutated EPHA2 were subjected to quantitative PCR (qPCR), western blot, immunoprecipitation (IP), and transwell migration assay. MG132 and chloroquine were used to inhibit the degradation of the WT and mutated EPHA2. The structural changes induced by rs137853199 were predicted and optimized using Schrödinger software. IP-mass spectrometry (IP-MS) was performed to examine the proteins that directly interact with WT and rs137853199 EPHA2. Sanger sequencing was performed to determine the frequency of rs137853199 in 184 patients with ARC (73 cortical cataracts, 56 nuclear cataracts, and 55 posterior subcapsular cataracts) and 49 normal controls. Results: Compared with the WT and the other three mutations, the rs137853199 mutation specifically resulted in a significant decrease in the expression of EPHA2. We identified that EPHA2 rs137853199 is degraded via the ubiquitin-proteasomal pathway through a lysine-48 (K48) residue linkage. Furthermore, the knockdown of EPHA2 reduced cell migration; while the overexpression of WT EPHA2 rescued this defect, the overexpression of rs137853199 EPHA2 did not. In addition, in cells overexpressing rs137853199 EPHA2, the expression of ß-catenin, a key protein that regulates cell migration, significantly decreased. We predicted that rs137853199 would induce a conformational change at a linker position in the carboxyl terminal of EPHA2. The IP-MS results showed that the main molecular functions of the proteins that specifically bind WT or rs137853199 EPHA2 are binding and catalysis, while the main protein class is the protein-modifying enzyme. Finally, we discovered that the minor allele frequency of rs137853199 was significantly higher in cortical cataract patients than it was in normal controls. Conclusions: In summary, these findings suggest a mechanism by which a point mutation in EPHA2 disrupts protein stability, expedites protein degradation, and decreases cell mobility. Importantly, this mutant is associated with cortical cataracts.


Assuntos
Catarata/genética , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/fisiologia , Cristalino/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Receptor EphA2/genética , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Catarata/fisiopatologia , Feminino , Humanos , Lentivirus/genética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
13.
Exp Eye Res ; 210: 108705, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34297945

RESUMO

Crystallins, the most prevalent lens proteins, have no turnover throughout the entire human lifespan. These long-lived proteins are susceptible to post-synthetic modifications, including oxidation and glycation, which are believed to be some of the primary mechanisms for age-related cataractogenesis. Thanks to high glutathione (GSH) and ascorbic acid (ASA) levels as well as low oxygen content, the human lens is able to maintain its transparency for several decades. Aging accumulates substantial changes in the human lens, including a decreased glutathione concentration, increased reactive oxygen species (ROS) formation, impaired antioxidative defense capacity, and increased redox-active metal ions, which induce glucose and ascorbic acid degradation and protein glycation. The glycated lens crystallins are either prone to UVA mediated free radical production or they attract metal ion binding, which can trigger additional protein oxidation and modification. This vicious cycle is expected to be exacerbated with older age or diabetic conditions. ASA serves as an antioxidant in the human lens under reducing conditions to protect the human lens from damage, but ASA converts to the pro-oxidative role and causes lens protein damage by ascorbylation in high oxidation or enriched redox-active metal ion conditions. This review is dedicated in honor of Dr. Frank Giblin, a great friend and superb scientist, whose pioneering and relentless work over the past 45 years has provided critical insight into lens redox regulation and glutathione homeostasis during aging and cataractogenesis.


Assuntos
Envelhecimento/fisiologia , Catarata/metabolismo , Glicosilação , Cristalino/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Animais , Ácido Ascórbico/farmacologia , Catarata/fisiopatologia , Cristalinas/metabolismo , Glutationa/metabolismo , Humanos , Cristalino/efeitos dos fármacos , Oxirredução , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo
14.
Exp Eye Res ; 209: 108645, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34087204

RESUMO

Lens-specific beaded filament (BF) proteins CP49 and filensin interact with the C-terminus of the water channel protein Aquaporin 0 (AQP0). Previously we have reported that a C-terminally end-deleted AQP0-expressing transgenic mouse model AQP0ΔC/ΔC developed abnormal optical aberrations in the lens. This investigation was undertaken to find out whether the total loss of the BF structural proteins alter the optical properties of the lens and cause optical aberrations similar to those in AQP0ΔC/ΔC lenses; also, to map the changes in the optical quality as a function of age in the single or double BF protein knockouts as well as to assess whether there is any significant change in the water channel function of AQP0 in these knockouts. A double knockout mouse (2xKO) model for CP49 and filensin was developed by crossing CP49-KO and filensin-KO mice. Wild type, CP49-KO, filensin-KO, and 2xKO lenses at different ages, and AQP0ΔC/ΔC lenses at postnatal day-17 were imaged through the optical axis and compared for optical quality and focusing property. All three knockout models showed loss of transparency, and development of abnormal optical distortion aberration similar to that in AQP0ΔC/ΔC. Copper grid focusing by the lenses at 6, 9 and 12 months of age showed an increase in aberrations as age advanced. With progression in age, the grid images produced by the lenses of all KO models showed a transition from a positive barrel distortion aberration to a pincushion distortion aberration with the formation of three distinct aberration zones similar to those produced by AQP0ΔC/ΔC lenses. Water permeability of fiber cell membrane vesicles prepared from CP49-KO, filensin-KO and 2xKO models, measured using the osmotic shrinking method, remained similar to that of the wild type without any statistically significant alteration (P > 0.05). Western blotting and quantification revealed the expression of comparable quantities of AQP0 in all three BF protein KOs. Our study reveals that loss of single or both beaded filament proteins significantly affect lens refractive index gradient, transparency and focusing ability in an age-dependent manner and the interaction of BF proteins with AQP0 is critical for the proper functioning of the lens. The presence of BF proteins is necessary to prevent abnormal optical aberrations and maintain homeostasis in the aging lens.


Assuntos
Aquaporinas/genética , Catarata/genética , Proteínas do Olho/genética , Regulação da Expressão Gênica , Proteínas de Filamentos Intermediários/genética , Cristalino/metabolismo , RNA/genética , Animais , Aquaporinas/biossíntese , Western Blotting , Catarata/metabolismo , Catarata/fisiopatologia , Modelos Animais de Doenças , Proteínas do Olho/biossíntese , Proteínas de Filamentos Intermediários/biossíntese , Cristalino/patologia , Cristalino/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
15.
Sci Rep ; 11(1): 12869, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145357

RESUMO

This study evaluated the accuracy of total keratometry (TK) and standard keratometry (K) for intraocular lens (IOL) power calculation in eyes treated with femtosecond laser-assisted cataract surgery. The retrospective study included a retrospective analysis of data from 62 patients (91 eyes) who underwent uneventful femtosecond laser-assisted cataract surgery with Artis PL E (Cristalens Industrie, Lannion, France) IOL implantation by a single surgeon between May 2020 and December 2020 in Severance Hospital, Seoul, South Korea. The new IOLMaster 700 biometry device (Carl Zeiss Meditec, Jena, Germany) was used to calculate TK and K. The mean absolute error (MAE), median absolute error (MedAE), and the percentages of eyes within prediction errors of ± 0.25 D, ± 0.50 D, and ± 1.00 D were calculated for all IOL formulas (SRK/T, Hoffer-Q, Haigis, Holladay 1, Holladay 2, and Barrett Universal II). There was strong agreement between K and TK (intraclass correlation coefficient = 0.99), with a mean difference of 0.04 D. For all formulas, MAE tended to be lower for TK than for K, and relatively lower MAE and MedAE values were observed for SRK/T and Holladay 1. Furthermore, for all formulas, a greater proportion of eyes fell within ± 0.25 D of the predicted postoperative spherical equivalent range in the TK group than in the K group. However, differences in MAEs, MedAEs, and percentages of eyes within the above prediction errors were not statistically significant. In conclusion, TK and K exhibit comparable performance for refractive prediction in eyes undergoing femtosecond laser-assisted cataract surgery.


Assuntos
Biometria , Extração de Catarata/métodos , Extração de Catarata/normas , Catarata/terapia , Cristalino/cirurgia , Lentes Intraoculares , Refração Ocular , Idoso , Idoso de 80 Anos ou mais , Catarata/fisiopatologia , Feminino , Humanos , Cristalino/fisiopatologia , Lentes Intraoculares/normas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Invest Ophthalmol Vis Sci ; 62(7): 23, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34156426

RESUMO

Purpose: The purpose of this study was to determine the importance of the xCT is a subunit. The cystine/glutamate antiporter is actually system xc-xCT subunit of the cystine/glutamate antiporter in maintaining redox balance by investigating the effects of the loss of xCT on lens transparency and cystine/cysteine balance in the aqueous humour. Methods: C57Bl/6 wild-type and xCT knockout mice at five age groups (6 weeks to 12 months) were used. Lens transparency was examined using a slit-lamp and morphological changes visualized by immunolabelling and confocal microscopy. Quantification of glutathione in lenses and cysteine and cystine levels in the aqueous was conducted by liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: Slit-lamp examinations revealed that 3-month-old wild-type mice and xCT knockout mice lenses exhibited an anterior localized cataract. The frequency of this cataract significantly increased in the knockout mice compared to the wild-type mice. Morphological studies revealed a localized swelling of the lens fiber cells at the anterior pole. Glutathione levels in whole lenses were similar between wild-type and knockout mice. However, glutathione levels were significantly decreased at 3 months in the knockout mice in the lens epithelium compared to the wild-type mice. Aqueous cysteine levels remained similar between wild-type and knockout mice at all age groups, whereas cystine levels were significantly increased in 3-, 9-, and 12-month-old knockout mice compared to wild-type mice. Conclusions: Loss of xCT resulted in the depletion of glutathione in the epithelium and an oxidative shift in the cysteine/cystine ratio of the aqueous. Together, these oxidative changes may contribute to the accelerated development of an anterior cataract in knockout mice, which appears to be a normal feature of aging in wild-type mice.


Assuntos
Envelhecimento/fisiologia , Humor Aquoso , Catarata , Cistina/metabolismo , Ácido Glutâmico/metabolismo , Cristalino , Animais , Antiporters/metabolismo , Humor Aquoso/diagnóstico por imagem , Humor Aquoso/fisiologia , Catarata/diagnóstico , Catarata/metabolismo , Catarata/fisiopatologia , Cristalino/diagnóstico por imagem , Cristalino/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal/métodos , Oxirredução , Estresse Oxidativo , Microscopia com Lâmpada de Fenda/métodos
17.
Acta Ophthalmol ; 99(7): e1013-e1017, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34080310

RESUMO

AIMS: To determine brake reaction times before and after bilateral cataract surgery in elderly drivers. METHODS: Sixty-four patients were evaluated on the day of and 4 weeks after bilateral cataract surgery. Forty-three healthy individuals with a valid driving licence served as the control group. A driving simulator was used to determine brake reaction times after receiving a visual stimulus. Total brake reaction time (BRT) as well as neurologic reaction time (NRT), foot transfer time (FTT) and brake pedal travel time (BPTT) were measured, and the measurements obtained before and after cataract surgery were compared. The correlations between NRT, best-corrected visual acuity (BCVA) and contrast sensitivity (CS) were assessed. RESULTS: Out of the 64 patients with bilateral cataract, 53 were assessed for postsurgical measurements. All time measures improved significantly after cataract surgery (BRT, 815.7(224) versus 647.9(148) ms; NRT, 364.7(91) versus 283.5(44) ms; FTT, 290.8(62) versus 248.6(58) ms; and BPTT, 160.6(96) versus 116.6(72) ms, p < 0.001). The calculated stopping distance improved significantly after surgery (22.3(6) versus 19.9(4) m at 50 km/h). Best-corrected visual acuity (BCVA) and contrast sensitivity (CS) improved significantly after surgery (0.25(0.2) versus 0.05(0.05), n = 53, p < 0.001; 1.4(0.2) versus 1.6(0.1), p < 0.001, respectively). There was a significant negative correlation between CS and NRT before surgery (r = -0.253, n = 64, p = 0.04, Pearson's correlation). CONCLUSION: Our findings show a significant effect of CS on neurological BRTs and the corresponding stopping distances. This highlights the importance of presurgical CS evaluation as a critical factor in cataract surgery decisions in elderly drivers.


Assuntos
Condução de Veículo/psicologia , Extração de Catarata , Catarata/psicologia , Sensibilidades de Contraste/fisiologia , Tempo de Reação/fisiologia , Idoso , Catarata/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Sci Rep ; 11(1): 11514, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075156

RESUMO

The aim of the study is to explore the distribution patterns and internal correlations of the morphological parameters of the cornea in patients with age-related cataract. The Pentacam HR was used to measure anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), total corneal astigmatism (TCA) and keratometric corneal astigmatism (KCA). With age, the proportion of with-the-rule (WTR) ACA decreased from 65.31% to 23.63%, while the against-the-rule (ATR) ACA increased from 26.53% to 56.20%. PCA exceeded 0.50 D in 9.14% of eyes, while 76.35% of them were ATR. The magnitude of ACA was positively correlated with PCA in the whole sample, with a more significant correlation in WTR eyes (sr = 0.349, P < 0.001). The vector summation effect of PCA to ACA changed from compensation to augmentation with aging. In 57.53% of WTR eyes, KCA was overestimated by an average of 0.21 ± 0.17 D, while it was underestimated by 0.38 ± 0.27 D in 87.62% of ATR eyes. In conclusion, among age-related cataract patients, ACA and TCA gradually shifted from WTR to ATR with aging, while most PCA remained as ATR. Ignoring the age-related changes and real PCA might cause overestimation of WTR astigmatism and underestimation of ATR astigmatism.


Assuntos
Envelhecimento/patologia , Astigmatismo , Catarata , Adulto , Idoso , Idoso de 80 Anos ou mais , Astigmatismo/etiologia , Astigmatismo/patologia , Astigmatismo/fisiopatologia , Catarata/complicações , Catarata/patologia , Catarata/fisiopatologia , Topografia da Córnea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
PLoS One ; 16(6): e0252102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077432

RESUMO

BACKGROUND: To explain the concept of the Castrop lens power calculation formula and show the application and results from a large dataset compared to classical formulae. METHODS: The Castrop vergence formula is based on a pseudophakic model eye with 4 refractive surfaces. This was compared against the SRKT, Hoffer-Q, Holladay1, simplified Haigis with 1 optimized constant and Haigis formula with 3 optimized constants. A large dataset of preoperative biometric values, lens power data and postoperative refraction data was split into training and test sets. The training data were used for formula constant optimization, and the test data for cross-validation. Constant optimization was performed for all formulae using nonlinear optimization, minimising root mean squared prediction error. RESULTS: The constants for all formulae were derived with the Levenberg-Marquardt algorithm. Applying these constants to the test data, the Castrop formula showed a slightly better performance compared to the classical formulae in terms of prediction error and absolute prediction error. Using the Castrop formula, the standard deviation of the prediction error was lowest at 0.45 dpt, and 95% of all eyes in the test data were within the limit of 0.9 dpt of prediction error. CONCLUSION: The calculation concept of the Castrop formula and one potential option for optimization of the 3 Castrop formula constants (C, H, and R) are presented. In a large dataset of 1452 data points the performance of the Castrop formula was slightly superior to the respective results of the classical formulae such as SRKT, Hoffer-Q, Holladay1 or Haigis.


Assuntos
Algoritmos , Biometria/métodos , Catarata/fisiopatologia , Lentes Intraoculares/normas , Óptica e Fotônica/métodos , Refração Ocular , Acuidade Visual/fisiologia , Humanos , Facoemulsificação , Período Pós-Operatório , Testes Visuais
20.
PLoS One ; 16(6): e0253210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34170915

RESUMO

BACKGROUND/AIMS: Determine the association between physician-deemed and patient-reported appropriateness and prioritization for cataract surgery. METHODS: Prospective cohort study of 471 patients of 7 ophthalmologists referred for cataract surgery. Ophthalmologists rated patients for cataract surgery appropriateness and prioritization using a visual analogue scale of 0-10 preoperatively. All patients completed the eCAPS Quality of Life (QoL), while 313 completed the Catquest-9SF and EQ-5D questionnaires. Regression analyses were applied to determine demographic, clinical and patient-reported outcome measures (PROMs) associated with appropriateness and prioritization. RESULTS: Two clinical factors (study eye and fellow eye best-corrected visual acuity (BCVA)), 2 eCAPS (night driving difficulty, ability to take care of local errands), and 2 Catquest-9SF PROMs (recognizing faces, seeing to walk on uneven ground) were associated with appropriateness. In multivariable regression, the rating physician, 2 clinical criteria (study eye BCVA, anticipated postoperative BCVA) and 1 eCAPS QoL (night driving difficulty) were associated with appropriateness. Prioritization was associated with low income, 8 clinical criteria, 9 eCAPS, 5 Catquest-9SF, and 1 EQ-5D PROMs. In multivariable regression, 1 clinical criterion (study eye BCVA), 2 eCAPS QoL (night driving difficulty, ability to take care of local errands), and 2 Catquest-9SF PROMs (seeing prices, seeing to walk on uneven ground) were significantly associated. CONCLUSIONS: The eCAPS and Catquest-9SF questionnaires show some concordance with physician-deemed appropriateness, and more with prioritization. Binary conversions of PROM scales provide similar modelling, with minimal loss of explanatory power. As physician-deemed appropriateness and prioritization do not completely capture the patient perspective, PROMs may have a role in cataract surgery decision-making frameworks.


Assuntos
Extração de Catarata , Catarata/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Médicos , Qualidade de Vida , Inquéritos e Questionários , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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