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PURPOSE: To analyze the refractive outcomes and safety of three-piece silicone toric sulcus-fixated add-on intraocular lenses (IOLs) (HumanOptics/Dr.Schmidt Intraocularlinsen, Erlangen, Germany) in complex clinical cases with high astigmatism such as in cases with previous penetrating keratoplasty. METHODS: Interventional case series of 21 eyes of 20 patients enrolled at two German centers. Functional results including power vector analysis, accuracy of IOL power calculation, rotational stability, and postoperative complications were evaluated from 2 months to 6 years postoperatively. RESULTS: The preoperative subjective cylinder exceeded or was equal to -6.00 diopters (D) in 81% of eyes (range: -2.00 to -17.00 D). The median follow-up period was 7.6 months (range: 57 days to 6 years). The efficacy analysis focused on the 2 to 6 months follow-up visit. Postoperatively, there was a median reduction of astigmatism by 70.59% (subjective cylinder range: 0.00 to -5.00 D), improvement of uncorrected distance visual acuity, and unchanged median corrected distance visual acuity. The attempted spherical equivalent was achieved within ± 0.50 D in 45% and within ± 1.00 D in 65% of cases. Five eyes received secondary surgical alignment of axis. Other complications related to the surgical procedure were mainly transient shortly after implantation, such as intraocular pressure elevation (2 of 21 eyes) or corneal edema (2 of 21 eyes). Persisting changes were seen only in rare cases and included pigment dispersion (1 of 21 eyes) or corneal edema requiring a second keratoplasty within 9 months after surgery (2 of 21 eyes). CONCLUSIONS: Toric add-on IOLs may be useful in reducing high astigmatism and anisometropia and increasing spectacle independence even in complex clinical conditions with high refractive errors.
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Astigmatismo/cirugía , Implantación de Lentes Intraoculares , Lentes Intraoculares , Elastómeros de Silicona , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Queratoplastia Penetrante , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Diseño de Prótesis , Refracción Ocular/fisiología , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To evaluate functional results and corneal changes after femtosecond laser correction of presbyopia (INTRACOR, Technolas Perfect Vision GmbH) in emmetropes using a modified treatment pattern over a 12-month period. METHODS: Twenty eyes from 20 emmetropic patients were treated with a modified intrastromal INTRACOR pattern consisting of 5 central rings and 8 radial cuts in a prospective, nonrandomized, uncontrolled, open, single-center, clinical study. Refraction, visual acuity, endothelial cell density, corneal pachymetry, total corneal power, and stray light were evaluated preoperatively and 1 (except endothelial cell density and stray light), 3, 6, and 12 months postoperatively. Patients filled out a subjective questionnaire at 12 months postoperatively. RESULTS: Comparison of preoperative versus 12-month postoperative median values revealed a significant improvement in uncorrected near visual acuity (UNVA) from 0.60 (20/80) to 0.10 logMAR (20/25) (P<.0001) and a significant decrease in corrected distance visual acuity (CDVA) from -0.10 (20/16) to 0.00 logMAR (20/20), which equals a median loss of one line (P=.0005). Fifteen percent of patients lost two lines of CDVA in the treated eye. Subjective spherical equivalent refraction remained unchanged at 0.00 diopters (D) (P=.194). After INTRACOR treatment, significant corneal steepening of 1.40 D and midperipheral flattening of 0.50 D occurred (both P<.0001). Corneal pachymetry at the thinnest point and endothelial cell density did not change significantly (P=.829 and P=.058, respectively). CONCLUSIONS: After 12 months, the modified INTRACOR pattern improved UNVA in emmetropic patients without inducing a myopic shift or significant changes in endothelial cell density or pachymetry.
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Sustancia Propia/cirugía , Aberración de Frente de Onda Corneal/fisiopatología , Emetropía/fisiología , Terapia por Láser/métodos , Presbiopía/cirugía , Aberrometría , Anciano , Recuento de Células , Paquimetría Corneal , Endotelio Corneal/patología , Femenino , Humanos , Luz , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Refracción Ocular/fisiología , Dispersión de Radiación , Encuestas y Cuestionarios , Agudeza Visual/fisiologíaRESUMEN
INTRODUCTION: Although alcohol dependence (AD) is highly prevalent, only few medications are approved for its treatment. While currently approved medications, such as naltrexone (NTX), reduce craving and relapse risk to a certain extent, new approaches are needed to complement these pharmaca. One potential compound is oxytocin (OXY), which proved beneficial effects on alcohol craving and stress reactivity in preliminary clinical studies and synergism with NTX effects. METHODS AND ANALYSIS: This clinical phase II trial is a monocentre two-armed, placebo (PLC)-controlled, 1:1 randomised, double-blind, parallel-group study. 62 participants with AD will be randomised to receive either intranasal OXY spray (24 IU) or PLC spray plus oral NTX (50 mg) for 2 days, and alcohol craving will be assessed using a validated combined stress-exposure and cue-exposure experiments and MRI. The primary outcome will be the intensity of alcohol craving, assessed using the Alcohol Urge Questionnaire (AUQ), 60 min after OXY/PLC application, directly after the stress and cue exposures. Secondary outcomes include subjective stress, negative affect, cortisol and OXY plasma levels, and neural response to alcohol and emotional cues and natural rewards. Follow-up drinking data were collected over 90 days. The primary efficacy analysis will test the difference between the verum and the PLC group in the distribution of AUQ craving scores. Appropriate statistical analysis will be used for the evaluation of the secondary outcomes. ETHICS AND DISSEMINATION: This trial has been approved by the ethics committee of Heidelberg University and competent authority. All participants in the trial will provide written informed consent. The study will be conducted according to the principles of the Declaration of Helsinki and in accordance to the German Medicinal Products act. Results of this study will be disseminated in peer-reviewed scientific journals and deidentified data, and the statistical analysis plan will be made available via open-access online repositories. TRIAL REGISTRATION NUMBERS: EudraCT 2021-003610-40 and NCT05093296.
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Alcoholismo , Naltrexona , Alcoholismo/tratamiento farmacológico , Alcoholismo/psicología , Ensayos Clínicos Fase II como Asunto , Ansia , Señales (Psicología) , Humanos , Naltrexona/farmacología , Naltrexona/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Oxitocina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: To evaluate the safety and efficacy of a new multi-segmented refractive multifocal intraocular lens (IOL) after phacoemulsification and refractive lens exchange (RLE). PATIENTS AND METHODS: In this prospective, multicenter clinical trial, 63 presbyopic subjects who had cataract or where RLE candidates were bilaterally implanted with the Precizon Presbyopia IOL (Ophtec BV, Groningen, the Netherlands) after phacoemulsification. The study was conducted at 6 clinical centers in Germany, the Netherlands, Belgium, Turkey and Spain. Subjects were evaluated at baseline and at 1 day, 1 week, 1 and 3 months postoperatively for monocular and binocular uncorrected (UDVA) and corrected distance visual acuity (CDVA), uncorrected (UIVA) and distance-corrected intermediate visual acuity (DCIVA), uncorrected (UNVA), corrected (CNVA) and distance-corrected near visual acuity (DCNVA), contrast sensitivity and quality of vision. RESULTS: Three months postoperatively, binocular UDVA and CDVA of ≥20/40 was achieved in 98.4% (60/61) and 100%, respectively. Binocular UIVA and DCIVA of ≥20/40 was achieved in 96.7% (59/61) and 93.4% (57/61) respectively. Binocular UNVA, CNVA and DCNVA of ≥20/40 was achieved in 93.4% (57/61), 98.4% (60/61) and 95% (57/60) subjects, respectively. Complete spectacle independence was achieved in 80% (49/61) patients; 93% of patients reported that they were quite or very satisfied with the outcomes of the procedure. CONCLUSION: Precizon Presbyopia IOL implantation is a safe and effective method to provide good visual acuity at all distances in presbyopic and cataract patients.
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PURPOSE: To elucidate the basis of the autosomal dominant congenital nuclear cataracts caused by the connexin50 mutant, CX50R23T, by determining its cellular distribution and functional behavior and the consequences of substituting other amino acids for arginine-23. METHODS: Connexin50 (CX50) mutants were generated by PCR and transfected into HeLa or N2a cells. Expressed CX50 protein was detected by immunoblot analysis and localized by immunofluorescence. Intercellular communication was assessed by microinjection of neurobiotin or by double whole-cell patch-clamp recording. RESULTS: HeLa cells stably transfected with CX50R23T or wild-type CX50 produced immunoreactive CX50 bands of identical electrophoretic mobility. Whereas HeLa cells stably expressing CX50 contained abundant gap junction plaques, CX50R23T localized predominantly in the cytoplasm. HeLa cells expressing wild-type CX50 showed large gap junctional conductances and extensive transfer of neurobiotin, but those expressing CX50R23T did not show significant intercellular communication by either assay. Moreover, CX50R23T inhibited the function of coexpressed wild-type CX50. Three CX50R23 substitution mutants (CX50R23K, CX50R23L, and CX50R23W) formed gap junction plaques, whereas two mutant substitutions with negatively charged residues (CX50R23D, CX50R23E) did not form detectable plaques. Only the mutant with a positive charge substitution (CX50R23K) allowed neurobiotin transfer at levels similar to those of wild-type CX50; none of the other mutants induced transfer. CONCLUSIONS: These results suggest that replacement of amino acid 23 in CX50 by any residue that is not positively charged would lead to cataract formation.
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Catarata/genética , Conexinas/genética , Proteínas del Ojo/genética , Mutación Puntual , Sustitución de Aminoácidos , Biotina/análogos & derivados , Biotina/metabolismo , Electrofisiología , Técnica del Anticuerpo Fluorescente Indirecta , Uniones Comunicantes/metabolismo , Regulación de la Expresión Génica/fisiología , Células HeLa/metabolismo , Humanos , Immunoblotting , Isoquinolinas/metabolismo , Microscopía Fluorescente , Mutagénesis Sitio-Dirigida , Reacción en Cadena de la Polimerasa , TransfecciónRESUMEN
PURPOSE: To evaluate the postoperative outcomes after implantation of a hydrophilic toric intraocular lens (tIOL) with a transitional conic toric surface in patients with astigmatism undergoing refractive lens exchange (RLE) or cataract surgery. METHODS: In this monocentric study, clinical outcomes following implantation of the hydrophilic Precizon toric IOL model 565 (Ophtec) were analysed. For intraoperative axis alignment, the Verion Image Guided System was used. Intended versus achieved refraction, IOL position, visual acuity outcomes and power vector analyses were evaluated 3 months postoperatively. RESULTS: Forty-three eyes of 28 patients (40 eyes cataract, 3 eyes RLE) received a Precizon toric IOL with a cylindrical power between 1.0 and 7.5 D. Target refraction was emmetropia except for four eyes that had a myopic target. The median postoperative IOL rotation at slit lamp was 3° with a range from 0° to 16°. Uncorrected distance visual acuity (UDVA) increased from median 0.5 logMAR preoperatively to median 0.06 logMAR at 3 months postoperatively. Corrected distance visual acuity increased from 0.20 to -0.02 logMAR. Median preoperative subjective cylinder was 1.5 D and 3 months postoperatively 0.25 D. CONCLUSION: Preoperative diagnostics, IOL selection and correct intraoperative positioning of tIOLs are essential for good outcomes and postoperative spectacle independence following cataract or RLE surgery. Visual acuities and rotational stability of the Precizon toric IOL showed very good outcomes and the subjective postoperative astigmatism could be reduced significantly.
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Implantación de Lentes Intraoculares , Lentes Intraoculares , Facoemulsificación/métodos , Seudofaquia/fisiopatología , Anciano , Astigmatismo/fisiopatología , Astigmatismo/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Periodo Posoperatorio , Estudios Prospectivos , Diseño de Prótesis , Refracción Ocular/fisiología , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento , Pruebas de Visión , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To determine the repeatability of keratometry of the Verion image-guided system and to compare the keratometry (K) values with those of established biometric devices. SETTING: International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. DESIGN: Prospective case series. METHODS: One randomly chosen eye of volunteers was examined with partial coherence interferometry (PCI) (IOLMaster 500), optical low-coherence reflectometry (OLCR) (Lenstar LS 900), a Scheimpflug device (Pentacam HR), and the new image-guided system by the same examiner. None of the eyes had ocular pathology. Three consecutive measurements were performed with the image-guided system and 1 with the other devices. The flat, steep, and average corneal radii; steep axis; and white-to-white (WTW) distance were analyzed and compared. RESULTS: One hundred twenty-three eyes of 123 volunteers (mean age 37.9 years ± 16.2 [SD]) had valid measurements for all examinations and were available for analysis. The image-guided system measured statistically significant smaller flat, steep, and average corneal radii than the Scheimpflug device, statistically significant larger flat and average corneal radii than the PCI device, and no statistically significant different values than the OLCR device. The measured steep axis did not differ significantly in any comparison. The WTW measurements were significantly higher than those of all other devices. The analysis of repeatability of the image-guided system showed high intraclass correlation coefficients (range 0.919 to 0.997). CONCLUSIONS: The new image-guided system had high repeatability for K, steep axis, and WTW measurements. The WTW measurements with the image-guided system were significantly higher than those using the other devices. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.
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Córnea/diagnóstico por imagen , Interferometría , Biometría , Alemania , Humanos , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To analyze the influence on intraocular lens (IOL) power calculation of corneal radii measured by the Verion Image-Guided System in comparison with those measured by partial coherence interferometry (PCI) (IOLMaster) and optical low-coherence reflectometry (OLCR) (Lenstar) systems. SETTING: International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. DESIGN: Prospective case series. METHODS: One eye of ophthalmologically healthy volunteers was examined with the image-guided, PCI, and OLCR systems. Corneal radii could be measured with all 3 devices; axial length (AL) and anterior chamber depth (ACD) could be measured with PCI and OLCR only. The IOL power calculations for the Acrysof SN60WF IOL using 4 formulas were compared between the image-guided system and both the PCI device and OLCR device. For IOL calculation with the image-guided system, the AL and ACD of the device used for comparison were applied. RESULTS: Of the 150 volunteers, 136 (mean age 39.60 years ± 17.31 [SD]) had valid measurements with all 3 devices and were included in the analysis. Compared with PCI, the image-guided system measured statistically significant larger values for corneal radii and IOL power calculations for all 4 formulas. There were no statistically significant differences between the image-guided system and the OLCR device. In both groups, the surgeon would have chosen the same IOL power in approximately 60% to 65% of cases and a ±0.5 diopter different IOL power in approximately 30% to 35% of cases when using the image-guided system. CONCLUSIONS: The IOL power calculation using the image-guided system showed statistically significant differences compared with the PCI device but not when compared with the OLCR device. The clinical relevance of this theoretical approach remains to be evaluated. FINANCIAL DISCLOSURE: Drs. Auffarth and Holzer received travel grants and lecture fees from Alcon Pharma GmbH and Carl Zeiss Meditec AG.
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Interferometría , Implantación de Lentes Intraoculares , Lentes Intraoculares , Biometría , Catarata , Alemania , Humanos , Óptica y Fotónica , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND/AIMS: To analyse visual outcomes and corneal changes 3â years after intrastromal femtosecond laser presbyopia treatment. METHODS: In a prospective, unicentric clinical trial, 25 presbyopic patients received INTRACOR treatment (Technolas femtosecond laser) on their non-dominant eye. Examinations were performed preoperatively as well as 1, 24 and 36â months postoperatively and included refraction, near, intermediate and distance visual acuity tests, reading speed, corneal topography, stray light measurement, endothelial cell count and slit-lamp examination. RESULTS: Comparison of preoperative versus 36â months postoperative values showed in median an improvement of uncorrected near visual acuity (UNVA) from 0.70 logMAR to 0.10 logMAR (p<0.001). Corrected distance visual acuity (CDVA) was reduced from -0.10 logMAR to 0.00 logMAR (p<0.001). The spherical equivalent preoperatively was 0.625â D and after an initial myopic shift after 1â month (0.125â D) and 24â months (0.25â D), the 36â months value (0.50â D) returned to resemble the preoperative value in statistical terms (p=0.123). A significant corneal steepening of 1.50â D in the treated area was measured. Pachymetry (thinnest point) revealed a statistically significant, but clinically insignificant corneal thickening from 535 to 549â µm (p=0.033). Endothelial cell count did not change. 92.86% of patients felt comfortable with the surgery result. CONCLUSION: INTRACOR treatment after 36â months improved UNVA to varying degrees. The effect can be explained by a corneal steepening. An initial myopic shift was reversible. Reductions especially in CDVA have to be taken into account and therefore careful patient selection and information is obligatory. TRIAL REGISTRATION NUMBER: NCT01164358 and NCT01025050, Results.
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Sustancia Propia/cirugía , Terapia por Láser/métodos , Presbiopía/cirugía , Refracción Ocular , Agudeza Visual , Anciano , Sustancia Propia/patología , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Presbiopía/diagnóstico , Presbiopía/fisiopatología , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To assess over a 36-month period functional results of the modified INTRACOR femtosecond laser-based intrastromal procedure to treat presbyopia. METHODS: 20 eyes of 20 presbyopic patients with mild hyperopia were included. The INTRACOR procedure with a modified pattern (six concentric intrastromal ring cuts) was performed using the FEMTEC femtosecond laser (Bausch+Lomb/Technolas Perfect Vision, Munich, Germany). Patients were also randomly divided into three subgroups to compare the effect of three different small inner ring diameters (1.8/2.0/2.2â mm (Groups A/B/C)). Follow-up examinations were performed at 1, 3, 6, 12, 24 and 36â months, and included near and distance visual acuity tests, slit-lamp examinations and corneal topography. RESULTS: Median uncorrected near visual acuity (UNVA) increased from 0.7/0.7/0.7 logMAR (Groups A/B/C) to -0.1/0.1/0.1 logMAR 36â months after surgery. Uncorrected distance visual acuity changed slightly from 0.1/0.2/0.1 logMAR to 0.2/0.3/0.1 logMAR. Losses of two lines of binocular corrected distance visual acuity (CDVA) were noted in 0/25/0% of eyes. Median spherical equivalent changed from 0.75/0.75/0.75 dioptres to -0.19/0.13/-0.19 dioptres. Overall patient satisfaction with the procedure was 80%. CONCLUSIONS: INTRACOR with a modified pattern improved UNVA in all patients over a 36-month follow-up period. The possibility of reduced CDVA underlines the need for careful patient selection. TRIAL REGISTRATION NUMBER: NCT00928122.
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Sustancia Propia/cirugía , Cirugía Laser de Córnea/métodos , Láseres de Excímeros/uso terapéutico , Presbiopía/cirugía , Refracción Ocular/fisiología , Agudeza Visual/fisiología , Anciano , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Presbiopía/fisiopatología , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
PURPOSE: The purpose of this study was to describe the visual prognosis as well as the frequency and clinical severity of central nervous system involvement in all acute posterior multifocal placoid pigment epitheliopathy (APMPPE) patients of one centre. METHODS: A retrospective database review of all patients and a prospective clinical, ophthalmological and neurological follow-up, if possible, were conducted. RESULTS: Eighteen patients with APMPPE were included with a mean follow-up of 17.1 months. Thirteen patients participated in a follow-up exam. Visual acuity improved in 9 of 18 patients to a mean of 0.17 log minimum angle of resolution (MAR) in the worse eye and remained stable in eight patients (mean, 0.03 logMAR). In the majority of patients, the 30° static perimetry improved at follow-up compared to the initial exams. Still, in up to 50 to 60 %, small visual field defects persisted. Overall, 11 patients (61 %) showed neurologic symptoms of varying severity. The most common neurological symptom was headache in nine (50 %) patients. Other symptoms included paraesthesias, psychosis, vertigo, and, as the most severe complication, stroke due to cerebral vasculitis. Fifteen patients were treated with systemic corticosteroids. CONCLUSIONS: Visual prognosis is good in patients with APMPPE, but visual field defects may remain. Neurological signs and symptoms, especially headaches, are frequent in APMPPE and should be taken seriously. Adequate investigations including MRI and CSF examination should be initiated in these patients.
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PURPOSE: To describe a severe case of keratomycosis caused by Arthrographis kalrae requiring repeated keratoplasty. METHODS: A 42-year-old otherwise healthy soft contact lens wearer developed a unilateral central corneal ulcer. Treatment with topical and systemic voriconazole is described. RESULTS: Repeated microbiological testing of ocular swabs (culture) initially yielded Candida albicans. Under treatment with topical clotrimazole, the ulcer progressed, and a corneal perforation required a keratoplasty à chaud. For prophylaxis, the patient received fluconazole systemically and continuous topical clotrimazole. However, in 2 weeks time, the mycotic infiltrates penetrated the corneal transplant and led to a second keratoplasty only 1 month after the first one. In the meantime, the microbiological analysis of the first keratoplasty revealed A. kalrae, which was sensitive to voriconazole. High-dose serum level-controlled systemic voriconazole and topical voriconazole were able to stabilize, but not eliminate the infection. About 1 year after the start of the voriconazole therapy, treatment had to be discontinued because of side effects. Mycotic infiltrates increased, and even an intracameral voriconazole injection could not prevent a third and a fourth keratoplasty. CONCLUSIONS: Ocular infection with A. kalrae is very rare. The microbiological differentiation of A. kalrae can be difficult. Because a broad spectrum of fungi is sensitive to voriconazole, the early topical and possibly systemic treatment is a reasonable therapeutic option when a mycotic infection of the eye is suspected, even before the causative fungus is identified.
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Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/microbiología , Hongos Mitospóricos/aislamiento & purificación , Micosis/microbiología , Adulto , Antifúngicos/uso terapéutico , Candida albicans/aislamiento & purificación , Lentes de Contacto Hidrofílicos , Perforación Corneal/metabolismo , Perforación Corneal/cirugía , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Femenino , Humanos , Queratoplastia Penetrante , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Pirimidinas/uso terapéutico , Reoperación , Triazoles/uso terapéutico , VoriconazolRESUMEN
The cytoplasmic N-termini of connexins have been implicated in protein trafficking, oligomerization and channel gating. To elucidate the role of the N-terminus in connexin37 (CX37), we studied mutant constructs containing partial deletions of its 23 N-terminal amino acids and a construct with a complete N-terminus in which residues 2-8 were replaced with alanines. All mutants containing nine or more N-terminal amino acids form gap junction plaques in transiently transfected HeLa cells, whereas most of the longer deletions do not. Although wild-type CX37 allowed intercellular transfer of microinjected neurobiotin in HeLa cells and formed conducting hemichannels in Xenopus oocytes, none of the mutant constructs tested show evidence of channel function. However, in coexpression experiments, N-terminal mutants that formed gap junction plaques potently inhibit hemichannel conductance of wild-type CX37 suggesting their co-oligomerization. We conclude that as much as half the length of the connexin N-terminus can be deleted without affecting formation of gap junction plaques, but an intact N-terminus is required for hemichannel gating and intercellular communication.