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PURPOSE: To analyze the accuracy of the current intraocular lens power calculation formulas using standard keratometry (K) and total keratometry (TK) data in patients with flat and steep corneas. DESIGN: Retrospective consecutive cross-sectional study. METHODS: An optical biometer with swept-source optical coherence tomography was used in this retrospective study. The standard deviation (SD), mean absolute error (MAE), median absolute error (MedAE), and the proportion of eyes with prediction error (PE) within ±0.25 diopter (D), ±0.5 D, ±0.75 D, and ±1.00 D were calculated to evaluate the refractive outcomes of each formula. RESULTS: A total of 231 eyes from 231 patients were included. In the entire study cohort, the Emmetropia Verifying Optical (EVO) formula using TK data showed the lowest SD (0.383) and MAE (0.30) and the highest percentage of cases with a PE within ±0.5 D (81.4%). In the flat keratometry group, the EVO (P = .042), Haigis (P = .043), Hoffer Q (P = .038) and Holladay 1 (P = .013) formulas using TK data had significantly lower SD than using K data. The EVO formula using TK data showed the lowest SD (0.357) and MAE (0.28). In the steep keratometry group, the Hoffer Q (P = .036) and SRK/T (P = .029) formulas using TK data had significantly lower SD than using K data. The BUII TK formula showed the lowest SD (0.431), MedAE (0.26), and MAE (0.32). CONCLUSION: The TK data set showed a better trend of refractive outcomes, especially in the flat and steep keratometry groups. EVO (TK) and BUII TK formulas were suggested for eyes with K values lower than 42 D and K values higher than 46 D, respectively.
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Lentes Intraoculares , Facoemulsificación , Humanos , Estudios Retrospectivos , Estudios Transversales , Facoemulsificación/métodos , Refracción Ocular , Córnea , Biometría/métodos , Óptica y Fotónica , Longitud Axial del OjoRESUMEN
Background: Preoperative evaluation of macular disorders is crucial to predict postoperative visual outcomes among patients with cataract. The swept-source optical coherence tomography (SS-OCT) based optical biometer was proved to be useful in screening macular pathology, while the impact of lens opacities and axial lengths on macular disease screening using SS-OCT based optical biometer remained unknown. This study aimed to evaluate the influence of lens opacities and axial lengths on foveal image quality detected by SS-OCT-based optical biometer, as well as sensitivity and specificity for the detection of macular diseases. Methods: This was a diagnostic accuracy study that retrospectively included patients who underwent preoperative cataract examinations at our hospital between November 2020 and June 2021. All patients underwent SS-OCT based optical biometer and spectral-domain OCT (SD-OCT). The SD-OCT was the golden standard for diagnosing macular diseases. Sensitivity, specificity, and receiver operating characteristic (ROC) were calculated to evaluate the value of foveal SS-OCT scans for the detection of macular disease. Results: Of the 224 eyes enrolled in the study, 82 eyes were diagnosed with macular disease by SD-OCT. The foveal image was almost indistinguishable due to poor quality when the mean grayscale of the image was less than 40. The posterior subcapsular opacity score and the axial length were significantly correlated with the gray density of the foveal image (r=-0.70, P<0.0001 and r=-0.40, P<0.0001). After excluding cases with indistinguishable foveal images (subcapsular opacities score ≥3.5, axial length ≥28.9 mm), the SS-OCT yielded 68% (95% confidence interval, 0.54-0.79) sensitivity and 87% (95% confidence interval, 0.78-0.92) specificity in 136 eyes. Conclusions: Routine SS-OCT based biometric measurement for the evaluation of macular pathology simultaneously prior to cataract surgery is suggested except for patients with advanced cataract (posterior subcapsular opacities score ≥3.5) and long axial length (≥28.9 mm).
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Purpose: Interleukin-6 (IL-6) is elevated in intraocular fluid from eyes with proliferative vitreoretinopathy (PVR), but the exact role of the cytokine is still unclear. We investigated the function and mechanism of IL-6 in retinal pigment epithelium (RPE) cell biology in vitro and in a mouse model in vivo. Methods: After treatment with various concentrations of IL-6, RPE cell proliferation was assessed with cell counting kit-8 (CCK-8) assay, and epithelial-mesenchymal transition (EMT) markers were evaluated using western blotting and immunofluorescent staining. The activation of JAK1/STAT3 signaling was determined with western blotting. Moreover, the effects of blockade of IL-6/JAK1/STAT3 signaling were investigated using pharmacological inhibitor S3I-201. For in vivo studies, the PVR model was induced with intravitreal injection of dispase/collagenase in wild-type and IL-6 knockout mice. The severity of PVR was evaluated with histological analysis. The expression of IL-6, gp130, and EMT markers was assessed with quantitative real-time PCR and western blotting. Results: IL-6 statistically significantly induced RPE cell proliferation and EMT in a dose-dependent manner in vitro, which was accompanied by rapid phosphorylation of JAK1 and STAT3. Blockade of the IL-6/JAK1/STAT3 pathway with S3I-201 apparently inhibited RPE proliferation and EMT. Furthermore, IL-6 and gp130 overexpression, and JAK1/STAT3 signaling hyperactivation were detected in the retinas of the wild-type mice at 1, 3, and 7 days after dispase/collagenase injection. Finally, we confirmed that IL-6 deficiency markedly alleviated mouse PVR development via inhibiting EMT. Conclusions: These findings indicate that IL-6 promotes PVR by inducing RPE proliferation and EMT via the JAK1/STAT3 signaling pathway. We provided new evidence that therapeutic strategies to block IL-6 may be beneficial for PVR.
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Transición Epitelial-Mesenquimal/genética , Interleucina-6/genética , Janus Quinasa 1/genética , Epitelio Pigmentado de la Retina/metabolismo , Factor de Transcripción STAT3/genética , Vitreorretinopatía Proliferativa/genética , Ácidos Aminosalicílicos/farmacología , Animales , Bencenosulfonatos/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Receptor gp130 de Citocinas/genética , Receptor gp130 de Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación de la Expresión Génica , Humanos , Interleucina-6/deficiencia , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 1/metabolismo , Ratones , Ratones Noqueados , Fosforilación/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Vitreorretinopatía Proliferativa/metabolismo , Vitreorretinopatía Proliferativa/patologíaRESUMEN
This corrects the article DOI: 10.1038/cdd.2016.152.
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Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial-mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFß2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.
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Cápsula Anterior del Cristalino/metabolismo , Catarata/genética , Células Epiteliales/metabolismo , Proteína Jagged-1/genética , MicroARNs/genética , Isoformas de Proteínas/genética , Receptor Notch1/genética , Animales , Cápsula Anterior del Cristalino/efectos de los fármacos , Cápsula Anterior del Cristalino/lesiones , Benzamidas/farmacología , Catarata/metabolismo , Catarata/patología , Catarata/terapia , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dioxoles/farmacología , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Fibrosis , Regulación de la Expresión Génica , Humanos , Proteína Jagged-1/metabolismo , Cristalino/efectos de los fármacos , Cristalino/metabolismo , Cristalino/patología , Ratones , MicroARNs/metabolismo , Análisis por Micromatrices , Oligorribonucleótidos/genética , Oligorribonucleótidos/metabolismo , Isoformas de Proteínas/metabolismo , Receptor Notch1/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta2/antagonistas & inhibidores , Factor de Crecimiento Transformador beta2/farmacología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The aim of this study was to evaluate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification cataract surgery (CPCS) in the treatment of cataract. Randomized controlled trials (RCTs) were searched in PubMed, Embase and the Cochrane Central Register of Controlled Trials. Nine qualified studies with a total of 989 eyes were included. Compared with CPCS, FLACS significantly reduced mean phaco energy and effective phacoemulsification time (EPT) required in the surgery. Central corneal thickness (CCT) was significantly lower in FLACS at 1 day of follow-up, but CCT and corneal endothelial cells count was comparable at 1 week of follow-up or longer. FLACS achieved a better visual outcome at postoperative 1 week and 6 months, but the difference was not significant at postoperative 1-3 months. Regard to surgical complications, the incidences of intraoperative anterior capsule tear, postoperative macular edema and elevated intraocular pressure were similar. In conclusion, femtosecond laser pretreatment can reduce phaco energy and EPT, which may reduce the heat damage to ocular tissues by ultrasound. This novel technique might be beneficial for patients with dense cataract and/or low preoperative endothelial cell values. Well-designed RCTs with longer follow-up are still necessary to provide more reliable evidence.
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Catarata/patología , Facoemulsificación , Capsulorrexis , Córnea/patología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the clinical use of optical coherence tomography (OCT) in optimizing surgical treatment strategies for conjunctivalized corneas secondary to ocular burns. METHODS: This noncomparative observational study included 25 patients with stable ocular burns and conjunctivalized corneas. OCT was performed on each eye. The thickness of corneal opacity or pseudopterygium and the underlying healthy stroma were measured. Individual surgical strategies were performed based on clinical examination and OCT images. RESULTS: Three types of conjunctivalized corneas were evaluated, including conjunctival pannus (4 of 25), pseudopterygium (10 of 25), and a white fibrovascular membrane (11 of 25). All 25 patients received a procedure of allograft limbal stem cell transplantation. In addition, with information provided in OCT images, 8 patients had combined lamellar keratoplasties; 3 patients had deep anterior lamellar keratoplasties, and 2 patients received penetrating keratoplasties. The remaining 12 patients received limbal stem cell transplantation alone. All fibrovascular tissues were successfully removed from the cornea in all patients. CONCLUSIONS: OCT is a valuable method in the evaluation of conjunctivalized corneas. This is helpful in determining the surgical treatments for individual patients, allowing for less corneal graft rejection and making good use of corneal donors.
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Quemaduras Químicas/patología , Enfermedades de la Conjuntiva/patología , Opacidad de la Córnea/patología , Quemaduras Oculares/inducido químicamente , Tomografía de Coherencia Óptica , Adolescente , Adulto , Aloinjertos , Quemaduras Químicas/cirugía , Niño , Preescolar , Enfermedades de la Conjuntiva/cirugía , Opacidad de la Córnea/cirugía , Quemaduras Oculares/cirugía , Femenino , Humanos , Queratoplastia Penetrante , Limbo de la Córnea/citología , Masculino , Estudios Prospectivos , Trasplante de Células Madre , Trasplante Autólogo , Adulto JovenRESUMEN
The mouse lens capsular injury model has been widely used in investigating the mechanisms of anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), and evaluating the efficacy of antifibrotic compounds. Nevertheless, there is no available protocol to quantitatively assess the treatment outcomes. Our aim is to describe a new method that can successfully quantify the wound and epithelial-mesenchymal transition (EMT) markers expression in vivo. In this model, lens anterior capsule was punctured with a hypodermic needle, which triggered lens epithelial cells (LECs) proliferation and EMT rapidly. Immunofluorescent staining of injured lens anterior capsule whole-mounts revealed the formation of ASC and high expression of EMT markers in the subcapsular plaques. A series of sectional images of lens capsule were acquired from laser scanning confocal microscopy (LSCM) three-dimensional (3D) scanning. Using LSCM Image Browser software, we can not only obtain high resolution stereo images to present the spatial structures of ASC, but also quantify the subcapsular plaques and EMT markers distribution successfully. Moreover, we also demonstrated that histone deacetylases (HDACs) inhibitor TSA significantly prevented injury-induced ASC using this method. Therefore, the present research provides a useful tool to study ASC and PCO biology as well as the efficacy of new therapies.
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Catarata , Proliferación Celular , Células Epiteliales , Transición Epitelial-Mesenquimal , Lesiones Oculares , Cristalino , Animales , Catarata/etiología , Catarata/metabolismo , Catarata/patología , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Lesiones Oculares/metabolismo , Lesiones Oculares/patología , Cristalino/lesiones , Cristalino/metabolismo , Cristalino/patología , RatonesRESUMEN
PURPOSE: To compare the effects of topical nonsteroidal anti-inflammatory drugs on pupil dilation maintenance during phacoemulsification cataract surgery and quantify the relationships between pupil size change and nuclear hardness. METHODS: This prospective randomized clinical observation study was single centered and double-masked. We studied 239 cases undergoing uneventful phacoemulsification cataract surgery in the absence of significant ocular comorbidity. Cases were randomly assigned to 1 of 6 groups receiving the following treatments: (1) diclofenac (0.1%); (2) pranoprofen (0.1%); (3) control, physiological normal saline solution; (4) diclofenac (0.1%) and epinephrine; (5) pranoprofen (0.1%) and epinephrine; (6) control, physiological normal saline and epinephrine solutions. Pupil diameter was measured at 3 intervals of cataract surgery: before the first incision, at the end of nucleus fragmentation, and at the end of cortex irrigation/aspiration. RESULTS: Compared with patients who were not treated, there was a significant difference in maintaining pupil dilation throughout the operation when the patients were treated with either diclofenac or pranoprofen, P<0.001 and P<0.03, respectively. From the first incision to postnucleus fragmentation, the change in pupil size in both diclofenac and control groups was significantly associated with the hardness of the crystalline lens, P=0.001 and P=0.012, respectively. At the end of irrigation/aspiration, the change in pupil size in only the control groups was significantly associated with the hardness of the crystalline lens, P=0.022. Diclofenac treatment was most effective at inhibiting pupil miosis when the hardness of the nucleus was grade 3, P=0.009. Pupil miosis was not related to the hardness of the nucleus when the patients were treated with epinephrine. CONCLUSIONS: Both diclofenac and pranoprofen treatment inhibit surgical-induced miosis. There is a negative correlation between the hardness of the crystalline lens and pupil diameter maintenance at the early stage of phacoemulsification.
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Antiinflamatorios no Esteroideos/administración & dosificación , Catarata/patología , Núcleo del Cristalino/patología , Midriáticos/administración & dosificación , Facoemulsificación/métodos , Pupila/efectos de los fármacos , Administración Oftálmica , Anciano , Benzopiranos/administración & dosificación , Diclofenaco/administración & dosificación , Método Doble Ciego , Epinefrina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miosis/prevención & control , Soluciones Oftálmicas/administración & dosificación , Propionatos/administración & dosificación , Estudios ProspectivosRESUMEN
Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is a major pathologic change in the development of proliferative vitreoretinopathy (PVR), which leads to severe visual impairment. ERK1/2 pathway has been reported to play a key role in the carcinogenesis, cancer metastasis, and multiple fibrotic diseases. We hypothesized that ERK1/2 signaling could cross-interact with transforming growth factor ß2 (TGFß2)/Smad and Notch signaling pathways in the regulation of EMT in RPE cells. Here, we demonstrated that ERK1/2 signaling was activated in TGFß2-induced EMT in human RPE cells, while blockade of the canonical TGFß2/Smad2/3 signaling with SB431542 could not inhibit TGFß2-induced the activation of ERK1/2. Meanwhile, blockade of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor U0126 strongly prevented TGFß2-induced the downregulation of P-cadherin, and the upregulation of α-SMA, collagen type IV, N-cadherin and fibronectin in RPE cells. In addition, we also identified that blockade of ERK1/2 signaling could inhibit not only the canonical TGFß/Smad signaling, but also the Jagged/Notch pathway. Finally, we found that blockade of Notch pathway with a specific inhibitor DAPT could inhibit TGFß2-induced the activation of ERK1/2 pathway conversely. Therefore, our study provides evidence that ERK1/2 signaling can cross-interact with the canonical TGFß/Smad and the Jagged/Notch signaling pathways in RPE cells EMT. ERK1/2 inhibitor may have therapeutic value in the prevention and treatment of PVR and other fibrotic diseases.
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Proteínas de Unión al Calcio/metabolismo , Células Epiteliales/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Receptores Notch/metabolismo , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta2/farmacología , Benzamidas/farmacología , Western Blotting , Butadienos/farmacología , Proteínas de Unión al Calcio/genética , Línea Celular , Dioxoles/farmacología , Inhibidores Enzimáticos/farmacología , Células Epiteliales/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína Jagged-1 , Proteínas de la Membrana/genética , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Complejos Multiproteicos/metabolismo , Nitrilos/farmacología , Receptor Notch3 , Receptores Notch/genética , Epitelio Pigmentado de la Retina/citología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Serrate-Jagged , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismoRESUMEN
Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is the major pathological mechanism in anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), which are important causes of visual impairment. Extracellular signal-regulated kinase (ERK)1/2 pathway has been reported to play a major role in carcinogenesis, cancer metastasis and various fibrotic diseases. We hypothesized that ERK1/2 signaling can cross-interact with canonical transforming growth factor ß (TGFß)/Smad signaling and the Notch pathway, which subsequently contributes to LECs EMT. In this study, we demonstrated that ERK1/2 signaling was activated in TGFß2-induced EMT in human LECs, whereas the blockade of TGFß2/Smad2/3 signaling with SB431542 did not inhibit the activation of ERK1/2 induced by TGFß2. In addition, inactivation of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor, U0126, completely prevented the TGFß2-induced upregulation of α-SMA, collagen type I, collagen type IV and fibronectin. We also demonstrated that inactivation of ERK1/2 signaling inhibited canonical TGFß/Smad signaling, as well as the Jagged/Notch pathway. By contrast, blockade of the Notch pathway by DAPT inhibited the TGFß2induced activation of ERK1/2 pathway in LECs. Thus, results of this study provide evidence for the complex interplay between ERK1/2, TGFß/Smad, and Jagged/Notch signaling pathways in the regulation of EMT in LECs. Inhibition of the ERK1/2 pathway may therefore have therapeutic value in the prevention and treatment of ASC and PCO.
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Proteínas de Unión al Calcio/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Butadienos/farmacología , Proteínas de Unión al Calcio/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína Jagged-1 , Proteínas de la Membrana/genética , Nitrilos/farmacología , Receptores Notch/genética , Receptores Notch/metabolismo , Proteínas Serrate-Jagged , Transducción de Señal/efectos de los fármacosRESUMEN
The epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays a key role in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), both of which lead to severe loss of vision. Recently, microRNAs (miRNAs) have been found to be involved in the regulation of various physiological and pathological processes, such as embryogenesis, organ development, oncogenesis and angiogenesis. However, the expression profile and function of miRNAs in the EMT of RPE cells remain to be clarified. In this study, human miRNA expression profiles were identified using microarrays and 304 miRNAs were found to be differentially expressed in TGFß2-induced EMT in human RPE cells. Of these differentially expressed miRNAs, 185 miRNAs were downregulated and 119 miRNAs were upregulated at least 2-fold in TGFß2 treatment samples. Similar alterations of miRNA expression were validated for 35 representative miRNAs by quantitative polymerase chain reaction analysis. Therefore, these results suggested that differentially expressed miRNAs play potential roles in TGFß2-induced EMT in RPE cells. This is an essential step in the identification of miRNAs associated with PVR and PDR progression, and in the identification of potential therapeutic targets for these diseases.
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Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , Epitelio Pigmentado de la Retina/citología , Factor de Crecimiento Transformador beta2/farmacología , Línea Celular , HumanosRESUMEN
The proliferation and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells are the major pathological changes in development of proliferative vitreoretinopathy (PVR), which leads to severe visual impairment. Histone deacetylases (HDACs)-mediated epigenetic mechanisms play important roles in controlling various physiological and pathological events. However, whether HDACs are involved in the regulation of proliferation and EMT in PRE cells remains unidentified. In this study, we evaluated the expression profile of HDAC family (18 genes) and found that some of class I and class II HDACs were up-regulated in transforming growth factor-ß2 (TGF-ß2)/TGF-ß1-stimulated RPE cells. Tricostatin A (TSA), a class I and II HDAC inhibitor, suppressed the proliferation of RPE cells by G1 phase cell cycle arrest through inhibition of cyclin/CDK/p-Rb and induction of p21 and p27. In the meantime, TSA strongly prevented TGF-ß2-induced morphological changes and the up-regulation of α-SMA, collagen type I, collagen type IV, fibronectin, Snail and Slug. We also demonstrated that TSA affected not only the canonical Smad signalling pathway but also the non-canonical TGF-ß/Akt, MAPK and ERK1/2 pathways. Finally, we found that the underlying mechanism of TSA affects EMT in RPE cells also through down-regulating the Jagged/Notch signalling pathway. Therefore, this study may provide a new insight into the pathogenesis of PVR, and suggests that epigenetic treatment with HDAC inhibitors may have therapeutic value in the prevention and treatment of PVR.
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Proliferación Celular/efectos de los fármacos , Inhibidores de Histona Desacetilasas/administración & dosificación , Ácidos Hidroxámicos/administración & dosificación , Epitelio Pigmentado de la Retina/crecimiento & desarrollo , Vitreorretinopatía Proliferativa/genética , Epigénesis Genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/administración & dosificación , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta2/administración & dosificación , Factor de Crecimiento Transformador beta2/genética , Vitreorretinopatía Proliferativa/patologíaRESUMEN
Congenital cataract is a major cause of visual impairment and childhood blindness. The solubility and stability of crystallin proteins play critical roles in maintaining the optical transparency of the lens during the life span. Previous studies have shown that approximately 8.3%~25% of congenital cataracts are inherited, and mutations in crystallins are the most common. In this study, we attempted to identify the genetic defect in a four-generation family affected with congenital cataracts. The congenital cataract phenotype of this four-generation family was identified as membranous cataract by slit-lamp photography. Mutation screening of the candidate genes detected a heterozygous c.465G â C change in the exon6 of the ßB2-crystallin gene (CRYBB2) in all family members affected with cataracts, resulting in the substitution of a highly conserved Tryptophan to Cystine (p.W151C). The mutation was confirmed by restriction fragment length polymorphism (RFLP) analysis and found that the transition resulted in the absence of a BslI restriction site in the affected members of the pedigree. The outcome of PolyPhen-2 and SIFT analysis predicted that this W151C mutation would probably damage to the structure and function of ßB2-crystallin. Wild type (wt) and W151C mutant ßB2-crystallin were expressed in human lens epithelial cells (HLECs), and the fluorescence results showed that Wt-ßB2-crystallin was evenly distributed throughout the cells, whereas approximately 34.7% of cells transfected with the W151C mutant ßB2-crystallin formed intracellular aggregates. Taken together, these data suggest that the missense mutation in CRYBB2 gene leads to progressive congenital membranous cataract by impacting the solubility and function of ßB2-crystallin.
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Catarata/congénito , Catarata/genética , Progresión de la Enfermedad , Mutación Missense , Cadena B de beta-Cristalina/química , Cadena B de beta-Cristalina/genética , Secuencia de Aminoácidos , Animales , Catarata/patología , Línea Celular , Núcleo Celular/metabolismo , Niño , Biología Computacional , Células Epiteliales/metabolismo , Femenino , Humanos , Cristalino/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fenotipo , Agregado de Proteínas , Alineación de Secuencia , Solubilidad , Cadena B de beta-Cristalina/metabolismoRESUMEN
PURPOSE: To investigate the paired box 6 (PAX6) gene in two sporadic patients from southern China presenting with classic aniridia. METHODS: The two sporadic patients underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from the leukocytes of the peripheral blood collected from the families of the two sporadic patients and 100 unrelated control subjects from the same population. Exons 4-13 of PAX6 were amplified by polymerase chain reaction (PCR) and sequenced directly. The ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, and Pentacam and Goldmann perimetry. RESULTS: The two patients were affected with aniridia accompanied by nystagmus. A heterozygous PAX6 frameshift mutation in exon 7, c.375_376delAG (p.Arg125SerfsX7), was identified in sporadic patient 1 and not in any of the unaffected family members and normal controls. One novel mutation in exon 10, c.868_871dupAGTT (p.Phe291X), was detected in sporadic patient 2. The frameshift mutation we identified has not previously been reported either in China or abroad. CONCLUSIONS: Although PAX6 mutations and polymorphisms have been reported in various ethnic groups, we report, for the first time, the identification of one new PAX6 mutation in Chinese aniridia patient.
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Aniridia/genética , Pueblo Asiatico/genética , Proteínas del Ojo/genética , Mutación del Sistema de Lectura , Proteínas de Homeodominio/genética , Nistagmo Congénito/genética , Factores de Transcripción Paired Box/genética , Proteínas Represoras/genética , Adulto , Aniridia/complicaciones , Secuencia de Bases , Niño , Exones , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Datos de Secuencia Molecular , Nistagmo Congénito/complicaciones , Factor de Transcripción PAX6 , Linaje , FenotipoRESUMEN
OBJECTIVE: Regular follow-up is essential to successful management of childhood cataract. We sought to assess whether a mobile phone short message service (SMS) for parents of children with cataract could improve follow-up adherence and the proportion of procedures performed in timely fashion. DESIGN: Randomized, controlled trial. This trial is registered with ClinicalTrials.gov, NCT01417819. PARTICIPANTS: We included 258 parent-child pairs involved in the Childhood Cataract Program of the Chinese Ministry of Health. METHODS: Participants were randomized (1:1) to a mobile phone SMS intervention or standard follow-up appointments. All participants were scheduled to attend ≥ 4 follow-up appointments according to the protocol. Parents in the intervention group received SMS automated reminders before scheduled appointments. The control group parents did not receive SMSs or any alternative reminder of scheduled appointments. Regular ocular examinations and analyses were performed by investigators masked to group allocation; however, study participants and the manager in charge of randomization and sending SMSs were not masked. MAIN OUTCOME MEASURES: Number of follow-up appointments attended, additional surgeries, laser treatments, changes in eyeglasses prescription, and occurrence of secondary ocular hypertension. RESULTS: Among parent-child participants, 135 were randomly assigned to the SMS intervention and 123 to standard appointments. Attendance rates for the SMS group (first visit, 97.8%; second, 91.9%; third, 92.6%; fourth, 83%) were significantly higher than those for the control group (first visit, 87.8%; second, 69.9%; third, 56.9%; fourth, 33.3%). The increase in attendance rate for total number of follow-up visits with SMS reminders was 47.2% (relative risk [RR] for attendance, 1.47; 95% confidence interval [CI], 1.16-1.78; P = 0.003). The number needed to remind (NNR) to gain 1 additional visit by 1 child was 3 (95% CI, 1.8-4.2). A total of 247 clinical interventions were carried out in the SMS group and 134 in the control group (RR, 1.68; 95% CI, 1.37-1.99; P = 0.007). The NNR to result in 1 additional clinical intervention was 5 (95% CI, 3.5-6.5). CONCLUSIONS: The SMS reminders significantly improved follow-up adherence in pediatric cataract treatment. Using readily available mobile phone resources may be an effective and economic strategy to improve management of childhood cataract in China. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Asunto(s)
Citas y Horarios , Catarata/terapia , Teléfono Celular/estadística & datos numéricos , Atención a la Salud/métodos , Cooperación del Paciente/estadística & datos numéricos , Sistemas Recordatorios , Envío de Mensajes de Texto , Adolescente , Opacificación Capsular/cirugía , Extracción de Catarata , Método Doble Ciego , Anteojos/estadística & datos numéricos , Femenino , Humanos , Terapia por Láser/estadística & datos numéricos , Masculino , Hipertensión Ocular/terapiaRESUMEN
PURPOSE: The purpose of this study was to investigate the fibroblast growth factor receptor 2 (FGFR2) gene in three Chinese patients with Crouzon syndrome and to characterize the related clinical features. METHODS: A single family underwent complete ophthalmic examinations, and three patients were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood collected from members of the family as well as from 100 unrelated control subjects from the same population. Exons 8 and 10 of FGFR 2 were amplified by polymerase chain reaction (PCR) and directly sequenced. We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, Pentacam, Goldmann perimetry, and computed tomography (CT) of the skull. RESULTS: The three patients were affected with shallow orbits and ocular proptosis, accompanied by mid-face hypoplasia and craniosynostosis, but had clinically normal hands and feet. A heterozygous FGFR2 missense mutation c.1030G>C (Ala344Pro) in exon 10 was identified in the affected individuals, but not in any of the unaffected family members or the normal controls. The mutation we identified has not previously been reported, either in China or abroad. CONCLUSIONS: Although FGFR2 mutations and polymorphisms have been reported in various ethnic groups, especially in the area of osteology, we report, for the first time, the identification of one new FGFR2 gene mutation in Chinese patients with Crouzon syndrome.
Asunto(s)
Pueblo Asiatico/genética , Disostosis Craneofacial/genética , Craneosinostosis/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Secuencia de Bases , Estudios de Casos y Controles , Niño , Disostosis Craneofacial/complicaciones , Disostosis Craneofacial/patología , Craneosinostosis/complicaciones , Craneosinostosis/patología , Exones , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación Missense , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Agudeza Visual , Adulto JovenRESUMEN
PURPOSE: The purposed of this study was to investigate the fibroblast growth factor receptor 2 (FGFR2) gene in one Chinese family with Crouzon syndrome and to characterize the related clinical features. METHODS: One family underwent complete ophthalmic examinations, and two patients were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood collected from the family and 100 unrelated control subjects from the same population. Exons 8 and 10 of FGFR2 were amplified by polymerase chain reaction (PCR) and directly sequenced. We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, Pentacam, Goldmann perimetry, and computed tomography (CT) of the skull. RESULTS: The two patients were affected with shallow orbits and ocular proptosis, accompanied by midface hypoplasia, craniosynostosis, and clinically normal hands and feet. A heterozygous FGFR2 missense mutation c.866A>C (Gln289Pro) in exon 8 was identified in the affected individuals, but not in any of the unaffected family members and the normal controls. CONCLUSIONS: Although FGFR2 mutations and polymorphisms have been reported in various ethnic groups, especially in the area of osteology, we report, for the first time, the identification of one new FGFR2 mutation in Chinese patients with Crouzon syndrome.
Asunto(s)
Disostosis Craneofacial/genética , Mutación Missense , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Adulto , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Secuencia de Bases , Niño , China , Análisis Mutacional de ADN , Cartilla de ADN/genética , Exones , Femenino , Heterocigoto , Humanos , Masculino , LinajeRESUMEN
PURPOSE: To investigate the paired box gene 6 (PAX6) in three patients from southern China presenting with classic aniridia: two patients from two successive generations of one family and one sporadic patient. METHODS: All the available members from two successive generations of one family and one sporadic patient underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from leukocytes of peripheral blood collected from the two generations of family members, the sporadic patient and 100 unrelated control subjects from the same population. Exons 1-13 of the PAX6 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. The ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, and Pentacam and Goldmann perimetry. RESULTS: The three patients were affected with aniridia accompanied by microcornea, microphthalmia, and nystagmus. A heterozygous PAX6 frameshift mutation, c.891del A(p.Gln297HisfsX68) in exon 10, was identified in the affected individuals and not in any of the unaffected family members, including the unaffected family members of the proband patient's generation. One novel mutation, c.607C>T(Arg203X) in exon 8, was detected in the unrelated sporadic patient. CONCLUSIONS: Although PAX6 gene mutations and polymorphisms have been reported from various ethnic groups, we report for the first time the identification of two new PAX6 gene mutations in Chinese aniridia patients.
Asunto(s)
Aniridia/genética , Proteínas del Ojo/genética , Proteínas de Homeodominio/genética , Factores de Transcripción Paired Box/genética , Proteínas Represoras/genética , Adulto , Segmento Anterior del Ojo/patología , Pueblo Asiatico/genética , Secuencia de Bases , China , Análisis Mutacional de ADN , Familia , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Factor de Transcripción PAX6 , LinajeRESUMEN
PURPOSE: To investigate the choroideremia (CHM) gene in two families with CHM and to characterize the related clinical features. METHODS: Two families underwent complete ophthalmic examinations and three males were diagnosed with CHM. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the two families and from 100 unrelated control subjects from the same population. Exons 1-15 of CHM were amplified by PCR and directly sequenced. Ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, visual field, optical coherence tomography, electroretinogram, and Pentacam. RESULTS: The affected men were hemizygous and had night blindness, chorioretinal atrophy spreading from the posterior pole to the mid-periphery, and bareness of the sclera. A novel c.1488delGinsATAAC mutation was detected in CHM in family 1. Another mutation c.1703 C>G (S558X) within exon 14 of CHM was identified in family 2, which caused the serine 558 codon (TCA) to be changed to a stop codon (TGA). CONCLUSIONS: This study identified a novel mutation in CHM associated with CHM and its related clinical features. Our findings expand the genotypic spectrum of CHM mutations associated with CHM and confirm the role of Rab escort protein-1 in the pathogenesis of CHM.