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1.
J Nutr ; 154(4): 1404-1413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432561

RESUMO

BACKGROUND: Blueberries and anthocyanins, their key bioactive component, may improve eye health. However, few long-term studies have examined blueberries and anthocyanins with cataract and age-related macular degeneration (AMD). OBJECTIVES: To investigate the prospective association between blueberry and anthocyanin intake with incident cataract, total AMD, and visually significant AMD among middle-aged and older women. METHODS: A total of 36,653 and 35,402 women initially free of AMD and cataract, respectively, aged ≥45 y from the Women's Health Study provided semiquantitative food frequency questionnaire data on blueberry intake categorized as none, 1-3 servings/mo, 1 serving/wk, or ≥2 servings/wk, plus a combined category of ≥1 serving/wk. Total anthocyanin intake and major subclasses were energy-adjusted and categorized into quintiles. Self-reported risk factors of eye disease were adjusted in multivariable hazard ratios (HRs) (95% confidence intervals [CIs]) of confirmed cataract, AMD, and visually significant AMD with mean follow-up of 11 y. RESULTS: Among the participants, 10.5% consumed ≥1 serving/wk of blueberries, with mean total anthocyanin intake of 11.2 mg/d. Compared to no blueberry intake, women consuming 1-3 servings/mo, 1 serving/wk, and ≥2 servings/wk had corresponding multivariable HRs of total AMD of 0.90 (95% CI: 0.73, 1.11), 0.71 (95% CI: 0.50, 1.00), and 0.36 (95% CI: 0.14, 0.93) (Ptrend = 0.011); those consuming ≥1 servings/wk had an HR of 0.68 (95% CI: 0.47, 0.98). A similar magnitude of HRs were found for visually significant AMD (Ptrend = 0.012) but not for cataract. There were no significant associations between increasing total anthocyanin quintiles and total and visually significant AMD, but there was a modest inverse association with cataract (Ptrend = 0.022), driven by a 10% reduction in cataract in the upper 2 quintiles. CONCLUSIONS: Greater blueberry intake significantly reduced total AMD, but not visually significant AMD or cataract. However, the magnitude of effect for visually significant AMD was similar to total AMD. There was a modest but significant inverse association between dietary anthocyanin intake with cataract but not AMD.


Assuntos
Mirtilos Azuis (Planta) , Catarata , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Antocianinas , Seguimentos , Fatores de Risco , Catarata/epidemiologia , Catarata/prevenção & controle
2.
J Biol Chem ; 298(10): 102417, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36037967

RESUMO

Γ-Crystallins play a major role in age-related lens transparency. Their destabilization by mutations and physical chemical insults are associated with cataract formation. Therefore, drugs that increase their stability should have anticataract properties. To this end, we screened 2560 Federal Drug Agency-approved drugs and natural compounds for their ability to suppress or worsen H2O2 and/or heat-mediated aggregation of bovine γ-crystallins. The top two drugs, closantel (C), an antihelminthic drug, and gambogic acid (G), a xanthonoid, attenuated thermal-induced protein unfolding and aggregation as shown by turbidimetry fluorescence spectroscopy dynamic light scattering and electron microscopy of human or mouse recombinant crystallins. Furthermore, binding studies using fluorescence inhibition and hydrophobic pocket-binding molecule bis-8-anilino-1-naphthalene sulfonic acid revealed static binding of C and G to hydrophobic sites with medium-to-low affinity. Molecular docking to HγD and other γ-crystallins revealed two binding sites, one in the "NC pocket" (residues 50-150) of HγD and one spanning the "NC tail" (residues 56-61 to 168-174 in the C-terminal domain). Multiple binding sites overlap with those of the protective mini αA-crystallin chaperone MAC peptide. Mechanistic studies using bis-8-anilino-1-naphthalene sulfonic acid as a proxy drug showed that it bound to MAC sites, improved Tm of both H2O2 oxidized and native human gamma D, and suppressed turbidity of oxidized HγD, most likely by trapping exposed hydrophobic sites. The extent to which these drugs act as α-crystallin mimetics and reduce cataract progression remains to be demonstrated. This study provides initial insights into binding properties of C and G to γ-crystallins.


Assuntos
Materiais Biomiméticos , Catarata , Cristalino , Chaperonas Moleculares , Agregação Patológica de Proteínas , Salicilanilidas , Xantonas , alfa-Cristalinas , gama-Cristalinas , Animais , Bovinos , Humanos , Camundongos , alfa-Cristalinas/metabolismo , Catarata/tratamento farmacológico , Catarata/prevenção & controle , Catarata/genética , gama-Cristalinas/metabolismo , Peróxido de Hidrogênio/metabolismo , Cristalino/metabolismo , Chaperonas Moleculares/metabolismo , Simulação de Acoplamento Molecular , Naftalenos/metabolismo , Ácidos Sulfônicos/metabolismo , Salicilanilidas/química , Salicilanilidas/farmacologia , Salicilanilidas/uso terapêutico , Xantonas/química , Xantonas/farmacologia , Xantonas/uso terapêutico , Agregação Patológica de Proteínas/tratamento farmacológico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/uso terapêutico
3.
J Fluoresc ; 33(4): 1347-1358, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36648626

RESUMO

The aggregation of lens proteins induced by glycation is one of the key drivers of diabetic retinopathy and development of diabetic cataracts. Moreover, glycation also causes numerous alterations not only to the tertiary structure of lens proteins but also to serum proteins. There are also evidences of covalent crosslinking among lens crystallins resulting in development of cataract. In this article, the inhibitory potential of butein was tested against the glucose induced glycation and the aggregation α-crystallin (α-cry). The results showed that there was inhibition of advanced glycation products (78.28%) and early glycation products (86.30%) following the treatment of butein. Additionally, the presence of butein caused a significant improvement in the tested biochemical markers of glycation. The treatment with butein reduced the free lysine modification to 23.67%. The secondary and tertiary structural distortions of α-cry were also protected. The mechanism of inhibition further investigated at the molecular level using biophysical and computational techniques. The interaction data showed the butein exhibited strong affinity towards the α-cry. The binding event was entropically driven and energetically favourable. The Gibb's free energy of the interaction was found to be -5.99 to -7.17 kcal mol-1. The binding site of butein in α-cry was deciphered by molecular docking and the dynamics was studied using molecular dynamics (MD) simulations. The simulation data showed that butein formed stable complex with α-cry under physiological conditions. Most of the tested parameters from molecular simulations, such as secondary structure, was found to be stable. The data clearly show the potential of butein in inhibiting the glycation induced aggregation of α-cry and hence can be developed as useful inhibitor in the management of diabetic cataract and retinopathy.


Assuntos
Catarata , Cristalinas , Diabetes Mellitus , Doenças Retinianas , alfa-Cristalinas , Humanos , alfa-Cristalinas/química , alfa-Cristalinas/metabolismo , Reação de Maillard , Simulação de Acoplamento Molecular , Glicosilação , Cristalinas/química , Cristalinas/metabolismo , Catarata/etiologia , Catarata/metabolismo , Catarata/prevenção & controle , Doenças Retinianas/complicações , Produtos Finais de Glicação Avançada/metabolismo
4.
Curr Opin Ophthalmol ; 34(3): 189-194, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36866844

RESUMO

PURPOSE OF REVIEW: There is a rising interest in the impact of diet on the pathogenesis of common ophthalmic conditions. The purpose of this review is to summarize the potential preventive and therapeutic power of dietary interventions described in recent basic science and epidemiological literature. RECENT FINDINGS: Basic science investigations have elucidated a variety of mechanisms by which diet may impact ophthalmic disease, particularly through its action on chronic oxidative stress, inflammation and macular pigmentation. Epidemiologic investigations have shown the real-world influence of diet on the incidence and progression of a number of ophthalmic diseases, particularly cataract, age-related macular degeneration (AMD) and diabetic retinopathy. A large observational cohort study found a 20% reduction in the incidence of cataract among vegetarians compared with nonvegetarians. Two recent systematic reviews found that higher adherence to Mediterranean dietary patterns was associated with a decreased risk of progression of AMD to later stages. Finally, large meta-analyses found that patients following plant-based and Mediterranean diets had significant reductions of mean haemoglobin A1c scores and incidence of diabetic retinopathy as compared with controls. SUMMARY: There is a significant and growing body of evidence that Mediterranean diet and plant-based diets - those that maximize fruits, vegetables, legumes, whole grains and nuts; and that minimize animal products and processed foods - help prevent vision loss from cataract, AMD and diabetic retinopathy. These diets may hold benefits for other ophthalmic conditions, as well. Nevertheless, there is a need for further randomized, controlled and longitudinal studies in this area.


Assuntos
Catarata , Retinopatia Diabética , Dieta Mediterrânea , Degeneração Macular , Animais , Humanos , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/prevenção & controle , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Degeneração Macular/prevenção & controle , Catarata/epidemiologia , Catarata/etiologia , Catarata/prevenção & controle , Estudos Observacionais como Assunto
5.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1936-1942, 2023 Apr.
Artigo em Zh | MEDLINE | ID: mdl-37282970

RESUMO

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.


Assuntos
Bibenzilas , Catarata , Cristalino , Humanos , Cristalino/metabolismo , Cristalino/patologia , Catarata/metabolismo , Catarata/patologia , Catarata/prevenção & controle , Bibenzilas/química , Bibenzilas/metabolismo , Bibenzilas/farmacologia , Células Epiteliais , Células Cultivadas , Apoptose
6.
Exp Eye Res ; 215: 108912, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34965405

RESUMO

Oxidative stress, generated because of an imbalance between reactive oxygen species (ROS) generation and elimination, is associated with lens damage and cataract progression. ROS generation is known to activate NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-cointaining 3) inflammasome, and is believed to be an important link between oxidative stress and inflammation, that is also related to cataract development. Potential oxidative hazard to the lens by white light-emitting diode (LED) light, a source of illumination commonly used nowadays, has been suggested, although available information is limited. In this work, we evaluated the cytotoxicity induced by hydrogen peroxide (an oxidative stressor agent) and white LED light in lens epithelial cells as well as melatonin ability to counteract the effects induced by them. Melatonin is a neurohormone secreted by different ocular structures that could be useful to alleviate oxidative damage induced by different oxidative stressors in lens. Particularly, the modulation of Nrf2 (nuclear erythroid 2-related factor)/Keap 1 (Kelch-like ECH-associated protein 1), an essential oxidative stress regulator, and NLRP3 activity by melatonin was evaluated in lens epithelial cells. ROS levels rose after white LED light exposure and cell viability was reduced after challenge with oxidative stressor agents. Melatonin prevented cell death triggered by hydrogen peroxide and white LED light, precluded ROS generation induced by white LED light and promoted antioxidant lens capacity through upregulation of Nrf2 protein levels and SOD activity. NLRP3, caspase-1 and IL1-ß expression significantly increased in human lens cells exposed to H2O2 or irradiated with white LED light. Activation of NLRP3 inflammasome triggered by oxidative stressors was also abrogated by melatonin. Attenuation of inflammatory and cytotoxic effects induced by oxidative stressors provided by melatonin in lens indicate the interest of this molecule as a potential therapeutic agent for cataract prevention/management.


Assuntos
Catarata , Melatonina , Catarata/metabolismo , Catarata/prevenção & controle , Humanos , Peróxido de Hidrogênio/toxicidade , Inflamassomos/metabolismo , Melatonina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
7.
Int J Med Sci ; 19(10): 1596-1602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185328

RESUMO

We aimed to investigate the association between habitual tea consumption and the risk of developing cataracts in a large community-based cohort study. We prospectively collected volunteers from 29 recruitment centers that were ≧ 55 years old with no history of cataracts at the beginning of the study. There were 12,080 participants with available information in our study and were divided into two groups according to habitual tea consumption; non-tea-drinking and tea-drinking groups. The mean age was 59 years. Compared to the non-tea-drinking group, the tea-drinking group had a significantly lower incidence of developing cataracts (15.5% vs 12.1%) during follow-up of 46 months. In multivariate Cox proportional hazards regression analysis, the relative risk (RR) of incident cataracts was lower in the tea-drinking group than the non-tea-drinking group (RR = 0.848; 95% confidence interval [CI] = 0.751 to 0.957). Participants with ≧ 2 cups per day were associated with almost 16% reduction in the risk of developing cataracts compared with the non-tea-drinking group (RR = 0.844; 95% CI = 0.741 to 0.961). Our study suggests that habitual tea consumption can reduce the incidence of cataracts and raises the possibility that the tea content may slow the progression of cataracts.


Assuntos
Catarata , Catarata/epidemiologia , Catarata/etiologia , Catarata/prevenção & controle , Estudos de Coortes , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Risco , Fatores de Risco
8.
J Sep Sci ; 45(13): 2406-2414, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35490347

RESUMO

Chrysanthemum is a kind of herb that can be used for both medicine and food. Although it has been shown to affect the redox damage of the lens, but the mechanism of action has not been systematically studied. This study identified the chemical profile of Fubai Chrysanthemum. Meanwhile, network pharmacology and the enrichment of the Kyoto Encyclopedia of Genes and Genomes pathway were combined to investigate the substance basis of Fubai Chrysanthemum for preventing cataract. The aqueous extracts of Fubaiju mainly contained 39 compounds. Compared with Gongju, Jinsiju, and wild chrysanthemum, Fubai Chrysanthemum showed a higher scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals and a higher content of total flavonoid. Fourteen chemical differences in four kinds of chrysanthemum were found based on principal component difference analysis. Pathway enrichment analysis showed that the main mechanisms of Fubai Chrysanthemum for preventing cataract were affecting the oxidative stress process and regulating cell growth and metabolism. Eventually, 11 key targets of Fubai Chrysanthemum for cataract prevention were identified. The strategy provided a better understanding of the chemical profile of Fubai Chrysanthemum and elucidated that its higher flavonoid content plays an important role in preventing cataract through antioxidant action and regulating cell growth.


Assuntos
Catarata , Chrysanthemum , Catarata/prevenção & controle , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Chrysanthemum/química , Flavonoides/farmacologia , Espectrometria de Massas , Farmacologia em Rede
9.
Drug Chem Toxicol ; 45(1): 170-179, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31547727

RESUMO

The present study was designed to determine protective effects of Coleus forskohlii hydroalcoholic leaf-extract along with its fractions against fructose-induced cataract rat model. The Coleus forskolii leaf extract was subjected to silica gel column chromatography and fractions were collected. A major high yielding fraction of the leaf extract, designated as fraction B6 was pharmacologically evaluated in Sprague Dawley albino rats at three doses 0.1, 1 and 10 mg/kg respectively. Compound B2; isolated from B6 fraction, identified as 'gallic acid' was also pharmacologically evaluated at three different doses. Cataract was induced by concurrent administration of fructose solution (10% w/v, per oral, dissolved in drinking water) for eight consecutive weeks. Mean arterial pressure, blood glucose level and lenticular opacity were determined. At the end of eight weeks, C. forskohlii leaf extract fraction and gallic acid reduced mean arterial pressure and glucose level in a dose dependent manner. In addition, C. forskohlii led to significant restoration of lens antioxidants enzyme level and reduced cataract formation in rats. These results showed the concentration dependent protective effect by C. forskohlii leaf extract against cataract formation due to restoration of oxidative stress markers.


Assuntos
Catarata , Plectranthus , Animais , Catarata/induzido quimicamente , Catarata/tratamento farmacológico , Catarata/prevenção & controle , Frutose/toxicidade , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
10.
Int J Mol Sci ; 23(16)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36012695

RESUMO

Cataract is the leading cause of blindness worldwide. A diverse range of medication has been invented to prevent or treat cataract. Pirenoxine (PRX), a drug with strong antioxidant properties, has been used topically to treat cataract, and there is much evidence to demonstrate the beneficial effects of PRX on lens opacity from in vitro and in vivo models. In clinical use, PRX has been prescribed worldwide by ophthalmologists for over six decades; however, there is still controversy with regard to its efficacy, and thus PRX remains an off-label use for cataract treatment. This comprehensive review summarizes and discusses evidence pertinent to the mechanisms of PRX and its efficacy mainly on cataract models. The issues that have been deemed uncertain over the six-decade use of PRX are examined. The information summarized in this review should provide insights into contriving novel approaches for the treatment of cataract.


Assuntos
Catarata , Cristalino , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Catarata/tratamento farmacológico , Catarata/etiologia , Catarata/prevenção & controle , Humanos , Oxazinas/farmacologia
11.
Int Ophthalmol ; 42(10): 3089-3095, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35378639

RESUMO

AIM: To retrospectively evaluate the effectiveness of the capsular vacuuming technique in reducing posterior capsule opacification (PCO). METHODS: Group 1 of the study consisted of 2752 eyes of 2752 patients with a cataract who had undergone phacoemulsification and IOL implantation surgery with anterior, equatorial, and posterior capsular polishing between January 2010 and December 2014. Group 2 consisted of 2761 eyes of 2761 patients with a cataract who had undergone phacoemulsification and IOL implantation surgery with anterior, equatorial, and posterior capsular polishing as well as posterior capsular vacuuming between January 2010 and December 2014. RESULTS: The mean patient age was 63.45 ± 12.23 years (range, 43-89) in Group 1 and 64.02 ± 13.36 years (range, 40-91) in Group 2. The two groups did not significantly differ with respect to age, sex, preoperative and postoperative uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) measurements (p > 0.05). At the 5-year follow-up, 253 eyes (9.19%) in Group 1 developed PCO requiring Nd:YAG laser capsulotomy, whereas 24 eyes (0.86%) in Group 2 developed PCO requiring Nd:YAG laser capsulotomy (p < 0.001). During capsular vacuuming, posterior capsule rupture was observed in the shape of a hole in only 2 eyes in Group 2. But the IOLs were implanted in the capsular bag in all eyes in both groups. CONCLUSION: PCO is the most common complication of cataract surgery; therefore, surgical technique is important in preventing PCO formation. We recommend posterior capsular vacuuming together with anterior, equatorial, and posterior capsular polishing, as this method significantly reduced the PCO rate.


Assuntos
Opacificação da Cápsula , Catarata , Lentes Intraoculares , Facoemulsificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/prevenção & controle , Opacificação da Cápsula/cirurgia , Catarata/etiologia , Catarata/prevenção & controle , Humanos , Implante de Lente Intraocular/efeitos adversos , Lentes Intraoculares/efeitos adversos , Pessoa de Meia-Idade , Facoemulsificação/efeitos adversos , Capsulotomia Posterior , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(12): 1754-1762, 2022 Dec 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-36748388

RESUMO

Posterior capsule opacification (PCO), a common complication after cataract surgery, impacts a patient's long-term visual quality to various degrees. Although a neodymium:yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy is a very effective treatment, it may lead to a serial of complications. Accordingly, the search for simple, safe, and effective methods to prevent PCO has received widespread attention. Various researchers are committed to the interdisciplinary collaboration between medicine and engineering fields, such as functionalizing the surface of the intraocular lens (IOL) via supercritical fluid impregnation, coating the surface of the IOL, high-concentration drug immersion, and application of a drug delivery system, to effectively reduce the incidence and severity of PCO.


Assuntos
Opacificação da Cápsula , Catarata , Cápsula do Cristalino , Lentes Intraoculares , Humanos , Opacificação da Cápsula/prevenção & controle , Opacificação da Cápsula/epidemiologia , Opacificação da Cápsula/cirurgia , Implante de Lente Intraocular , Catarata/prevenção & controle , Catarata/etiologia , Cápsula do Cristalino/cirurgia , Lentes Intraoculares/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias , Desenho de Prótese
13.
Exp Eye Res ; 205: 108485, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33582182

RESUMO

The pathogenesis of congenital cataract (CC), a major disease associated with blindness in infants, is complex and diverse. Aquaporin 5 (AQP5) represents an essential membrane water channel. In the present study, whole exome sequencing revealed a novel heterozygous missense mutation of AQP5 (c.152 T > C, p. L51P) in the four generations of the autosomal dominant CC (adCC) family. By constructing a mouse model of AQP5 knockout (KO) using the CRISPR/Cas9 technology, we observed that the lens of AQP5-KO mice showed mild opacity at approximately six months of age. miR-124-3p.1 expression was identified to be downregulated in the lens of AQP5-KO mice as evidenced by qRT-PCR analysis. A dual luciferase reporter assay confirmed that vimentin was a target gene of miR-124-3p.1. Organ-cultured AQP5-KO mouse lenses were showed increased opacity compared to those of WT mice, and vimentin expression was upregulated as determined by RT-PCR, western blotting, and immunofluorescence staining. After miR-124-3p.1 agomir was added, the lens opacity in WT mice and AQP5-KO mice decreased, accompanied by the downregulation of vimentin. AQP5-L51P increased vimentin expression of in human lens epithelial cells. Therefore, a missense mutation in AQP5 (c.152 T > C, p. L51P) was associated with adCC, and AQP5 could participate in the maintenance of lens transparency by regulating vimentin expression via miR-124-3p.1.


Assuntos
Aquaporina 5/fisiologia , Catarata/prevenção & controle , Regulação da Expressão Gênica/fisiologia , Cristalino/metabolismo , MicroRNAs/genética , Vimentina/genética , Adulto , Idoso , Animais , Western Blotting , Catarata/genética , Catarata/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase em Tempo Real
14.
Exp Eye Res ; 202: 108319, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080303

RESUMO

The purpose of this study was to investigate whether and how topical nerve growth factor (NGF) attenuates streptozotocin (STZ)-induced diabetic cataracts in vivo. Rats were randomly divided into three groups, including the normal control rat group, STZ-induced diabetic cataract rat group (DM group), and STZ-induced diabetic cataract rat group treated with 200 µg/mL recombinant rat ß-NGF (DM + NGF group). Cataract formation was evaluated by portable slit lamp biomicroscopy following pupil dilation at 8 weeks. The expression levels of NGF, aldose reductase (AR), and Na+/K+-ATPase in the lens epithelial cells (LECs) of the three groups were measured in the presence or absence of topical NGF. TUNEL-positive LECs were quantified to determine if hyperglycemia caused LEC apoptosis. At 8 weeks, the mean cataract score in the control group was significantly lower than that in DM and DM + NGF groups, and the score in the DM + NGF group was significantly lower than that in the DM group. At the equatorial zone and anterior central zone of lens, NGF and Na+/K+-ATPase expression levels were significantly decreased in the DM group; however, they were partially restored in the DM + NGF group. At the equatorial zone and anterior central zone of lens, AR expression and TUNEL-positive apoptotic LECs were significantly increased in the DM group compared with the control group, however, they were significantly decreased in the DM + NGF group. In conclusion, topical NGF could delay the progression of diabetic cataracts by attenuating polyol pathway activation and increasing Na+/K+-ATPase protein levels.


Assuntos
Catarata/prevenção & controle , Diabetes Mellitus Experimental/prevenção & controle , Fator de Crescimento Neural/uso terapêutico , ATPase Trocadora de Sódio-Potássio/metabolismo , Administração Oftálmica , Animais , Apoptose , Catarata/induzido quimicamente , Catarata/enzimologia , Catarata/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/patologia , Hiperglicemia/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Soluções Oftálmicas , Polímeros , Ratos , Ratos Sprague-Dawley , Estreptozocina/toxicidade , Regulação para Cima
15.
Bioorg Chem ; 114: 104970, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34120026

RESUMO

Thiazolidinediones (TZD), benzopyrans are the proven scaffolds for inhibiting Aldose reductase (ALR2) activity and their structural confluence with the retention of necessary fragments helped in designing a series of hybrid compounds 2-(5-cycloalkylidene-2,4-dioxothiazolidin-3-yl)-N-(2-oxo-2H-chromen-3-yl)acetamide (10a-n) for better ALR2 inhibition. The compounds were synthesized by treating substituted 3-(N-bromoacetyl amino)coumarins (9a-d) with potassium salt of 5-cyclo alkylidene-1,3-thiazolidine-2,4-diones (4a-d). The inhibition activity against ALR2 with IC50 values range from 0.012 ± 0.001 to 0.056 ± 0.007 µM. N-[(6-Bromo-3-coumarinyl)-2-(5-cyclopentylidene-2,4-dioxothiazolidin-3-yl)] acetamide (10c) with cyclopentylidene group on one end and the 6-bromo group on the other end showed better inhibitory property (IC50 = 0.012 µM) and selectivity index (324.166) against the ALR2, a forty fold superiority over sorbinil, a better molecule over epalrestat and rest of the analogues exhibited a far superior response over sorbinil and slightly better as compared with epalrestat. It was further confirmed by the insilico studies that compound 10c showed best inhibition activity among the synthesized compounds with a high selectivity index against the ALR2. In invivo experiments, supplementation of compound 10c to STZ induced rats delayed the progression of cataract in a dose-dependent manner warranting its further development as a potential agent to treat thediabetic secondary complications especially cataract.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Cumarínicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Tiazolidinedionas/uso terapêutico , Aldeído Redutase/metabolismo , Animais , Catarata/prevenção & controle , Cumarínicos/síntese química , Cumarínicos/metabolismo , Cumarínicos/farmacocinética , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacocinética , Hipoglicemiantes/síntese química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacocinética , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Tiazolidinedionas/síntese química , Tiazolidinedionas/metabolismo , Tiazolidinedionas/farmacocinética
16.
J Epidemiol ; 31(1): 21-29, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31839643

RESUMO

BACKGROUND: Although the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan. METHODS: This study included 32,387 men and 39,333 women aged 45-74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after 5-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors. RESULTS: We identified 1,836 incident cataracts in 594 men and 1,242 women. In men, the OR for cataract was decreased with higher intake of vegetables (ORQ5 vs Q1, 0.77; 95% confidence interval [CI], 0.59-1.01; Ptrend across quartile categories = 0.03) and cruciferous vegetables (ORQ5 vs Q1, 0.74; 95% CI, 0.57-0.96; Ptrend = 0.02). In contrast, the OR for cataract was increased with higher intake of vegetables among women (ORQ5 vs Q1, 1.28; 95% CI, 1.06-1.53; Ptrend = 0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex. CONCLUSIONS: This study suggests that vegetables may reduce the risk of cataract in men, but not in women.


Assuntos
Catarata/epidemiologia , Catarata/prevenção & controle , Frutas , Verduras , Adulto , Idoso , Dieta , Inquéritos sobre Dietas , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
17.
Zhonghua Yan Ke Za Zhi ; 57(1): 17-22, 2021 Jan 11.
Artigo em Zh | MEDLINE | ID: mdl-33412639

RESUMO

Dry eye is a common ocular surface disease that can occur in part of patients before cataract surgery. A variety of incentives during the perioperative period can decrease the stability of the tear film, cause or aggravate dry eye symptoms, and therefore reduce the visual outcome and life quality of the patients. In order to standardize the management of dry eye during the perioperative period of cataract surgery, the Cataract Group of the Ophthalmology Branch of the Chinese Medical Association conducted a comprehensive discussion on the evaluation and improvement of the preoperative ocular surface conditions, the intraoperative ocular surface protection, as well as the diagnosis and treatment of postoperative dry eye. The consensus of opinions has been reached for reference of Chinese ophthalmologists. (Chin J Ophthalmol, 2021, 57:17-22).


Assuntos
Catarata , Síndromes do Olho Seco , Oftalmologia , Povo Asiático , Catarata/prevenção & controle , Consenso , Síndromes do Olho Seco/prevenção & controle , Humanos , Período Perioperatório
18.
Zhonghua Yan Ke Za Zhi ; 57(7): 492-494, 2021 Jul 11.
Artigo em Zh | MEDLINE | ID: mdl-34256468

RESUMO

Posterior capsular opacification (PCO) is the most common complication that leads to vision loss after cataract surgery. It is classically divided into fibrotic type and regenerative type according to clinical manifestations or pathological mechanisms. The widely used technique for preventing PCO is to mechanically polish anterior and posterior capsules after an uneventful phacoemulsification surgery. However, the efficacy of polishing anterior capsules on prevention of PCO is debatable. It has been found that polishing anterior capsules has an inhibitory or no effect on fibrotic PCO, but a stimulating effect on regenerative PCO. Therefore, whether to polish anterior capsules is dependent on the condition of individual patients and the type of intraocular lenses. (Chin J Ophthalmol, 2021, 57: 492-494).


Assuntos
Opacificação da Cápsula , Catarata , Cápsula do Cristalino , Lentes Intraoculares , Facoemulsificação , Opacificação da Cápsula/prevenção & controle , Catarata/prevenção & controle , Humanos , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular , Polônia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Desenho de Prótese
19.
Biochem Biophys Res Commun ; 533(4): 1255-1261, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33066958

RESUMO

Oxidative stress is one of the most important risk factors for cataractogenesis. Previous studies have indicated that BDS-II, a Kv3 channel blocker, plays pivotal roles in oxidative stress-related diseases. This study demonstrates that BDS-II exerts a protective effect on cataractogenesis. Specifically, BDS-II was observed to inhibit lens opacity induced by H2O2. BDS-II was also determined to inhibit cataract progression in a sodium selenite-induced in vivo cataract model by inhibiting reduction of the total GSH. In addition, BDS-II was demonstrated to protect human lens epithelial cells against H2O2-induced cell death. Our results suggest that BDS-II is a potential pharmacological candidate in cataract therapy.


Assuntos
Catarata/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/uso terapêutico , Canais de Potássio Shaw/antagonistas & inibidores , Animais , Morte Celular , Linhagem Celular , Progressão da Doença , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Cristalino/citologia , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Ratos Sprague-Dawley , Canais de Potássio Shaw/metabolismo
20.
J Biochem Mol Toxicol ; 34(1): e22420, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746523

RESUMO

Oxidative stress-induced toxicity plays a major role in ocular diseases such as retinal degeneration, age-related cataract (ARC) formation and macular dystrophy. In this study, we explored the possible role of resveratrol (RSV) at the different dose levels (10, 20 and 40 mg/kg/day, ip) in an experimental model of naphthalene (1 g/kg/day, po)-induced age-related cataracts. Morphological changes in the eyes of the rats in two groups, the RSV and the ARC groups, were monitored weekly, and biochemical parameters in the lenses were assessed after completion of the experimental work. A comparison between the rats in the two groups showed that treatments at RSV doses of 20 and 40 mg/kg/day significantly retarded lenticular opacity, restored antioxidants (CAT, SOD, GPX, GSH), Ca2+ ATPase function, and protein contents, and reduced lipid peroxidation in the lenses of the animals in the RSV group. The treatment with resveratrol at a dose of 10 mg/kg/day did not show any anti-cataractogenic effects. Based on the results of our investigation, we conclude that supplemental doses of resveratrol at 40 mg/kg/day effectively prevent cataract formation associated with the aging via increased soluble protein contents and Ca2+ homeostasis, apart from the antioxidant restoration. The results demonstrate that RSV treatment may be considered as a promising preventive or supplemental measure for delaying and/or preventing the formation of ARCs.


Assuntos
Catarata/induzido quimicamente , Catarata/prevenção & controle , Naftalenos/toxicidade , Resveratrol/farmacologia , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley , Resveratrol/administração & dosagem
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