A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration

Carotenoides; Marcadors inflamatoris; Àcids grassos poliinsaturatsCarotenoides; Marcadores inflamatorios; Ácidos grasos poliinsaturadosCarotenoids; Inflammatory markers; Polyunsaturated fatty acidsThe purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of −1.63 (95% CI −0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.The research was funded by Laboratorios Théa (Barcelona, Spain) and by research grants from the “Instituto de Salud Carlos III/European Regional Development Fund (ERDF)” and RD16/0008/0011, OFTARED: Enfermedades oculares: “Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares”

Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD

Purpose: To evaluate the therapeutic effect of subconjunctival injection of human mesenchymal stromal cells (hMSCs) in the cornea of mice with graft versus host disease (GVHD). Methods: GVHD was induced in mice after hematopoietic stem cell transplantation (HSCT) between MHC-mismatched mouse strains. Subconjunctival injection of hMSCs was applied at day 10 post-HSCT. Infiltration of CD3+ cells in the cornea and epithelial alterations were analyzed by immunofluorescence. Tear was assessed using the PRT test and TearLab Osmolarity System. qPCR was used to evaluate changes in cytokines, Pax6 and Sprr1b expression. To evaluate the effect of irradiation, we analyzed the expression of these genes in TBI mice. Results: Immune cell invasion occurs in mice with GVHD, as shown by the presence of CD3+ cells in the cornea. Interestingly, eyes treated with hMSC did not present CD3+ cells. Tear osmolarity was increased in GVHD eyes, but not in treated eyes. TNFa expression was highly increased in all corneas except in Control and treated eyes. Pax6 in corneal epithelium showed a similar pattern in GVHD and Control mice, and its gene expression was enhanced in GVHD corneas. In contrast, Pax6 was reduced in GVHD + MSC corneas. We also found an increase in SPRR1B staining in GVHD eyes that was lower in GVHD + MSC mice, demonstrating that corneal keratinization is less frequent after treatment with hMSC. Conclusions: The treatment with hMSCs by subconjunctival injection is effective in reducing corneal inflammation and squamous metaplasia in ocular GVHD (oGVHD). Local treatment with hMSCs is a promising strategy for oGVHD.This study was supported by Fund for Health of Spain (FIS) grant PI12/00939 and Red de Terapia Celular de Castilla y León. Rafael Martínez-Carrasco was supported by a grant from Junta de Castilla y León. A. Velasco, J. Aijón and E. Hernández-Galilea belong to UIC.077 and L.I. Sánchez-Abarca and F. Sánchez-Guijo to UIC-116 from Junta de Castilla y León

Human Bone Marrow Stromal Cells Differentiate Into Corneal Tissue and Prevent Ocular Graft-Versus-Host Disease in Mice

Clinical trials have assessed the use of human bone marrow stromal cells (hBMSCs) for the treatment of immune-related disorders such as graft-versus-host disease (GVHD). In the current study, we show that GFP+-transduced hBMSCs generated from bone marrow migrate and differentiate into corneal tissue after subconjunctival injection in mice. Interestingly, these hBMSCs display morphological features of epithelial, stromal, and endothelial cells and appear at different layers and with different morphologies depending on their position within the epithelium. Furthermore, these cells display ultrastructural properties, such as bundles of intermediate filaments, interdigitations, and desmosomes with GFP- cells, which confirms their differentiation into corneal tissues. GFP+-transduced hBMSCs were injected at different time points into the right eye of lethally irradiated mice undergoing bone marrow transplantation, which developed ocular GVHD (oGVHD). Remarkably, hBMSCs massively migrate to corneal tissues after subconjunctival injection. Both macroscopic and histopathological examination showed minimal or no evidence of GVHD in the right eye, while the left eye, where no hBMSCs were injected, displayed features of GVHD. Thus, in the current study, we confirm that hBMSCs may induce their therapeutic effect at least in part by differentiation and regeneration of damaged tissues in the host. Our results provide experimental evidence that hBMSCs represent a potential cellular therapy to attenuate oGVHD

Horizontal gaze palsy following intraoral local anesthesia, a first manifestation of multiple sclerosis

Introduction: Different type of anesthesia has been implicated in the exacerbation of multiple sclerosis. Moreover, dental anesthesia is related to ophthalmologic complications such as diplopia due to oculomotor nerves palsy. Various pathophysiologic mechanisms are discussed: intravascular (arterial/vein) injection of anesthetic, reflex vasospasm and diffusion of local anesthetic. Case report: A 36-year-old woman who presented an horizontal left gaze palsy, bilateral nystagmus in extreme gaze and left peripheral facial palsy after dental anesthesia. The patient recovered peripheral facial palsy within 3 h after the injection. As a result of the magnetic resonance, it was initiated high doses systemic corticosteroid treatment and the gaze palsy resolved within three weeks. The patient was diagnosed with peripheral facial palsy secondary to dental anesthesia and multiple sclerosis. Conclusion: The concomitance of symptoms with local anesthesia complicates the etiological diagnosis of pathology, so exhaustive and detailed exam taking into consideration all factors is necessary for a proper diagnosis and treatment

Scribble basal polarity acquisition in RPE cells and its mislocalization in a pathological AMD-like model

Apicobasal polarity is a hallmark of retinal pigment epithelium cells and is required to perform their functions; however, the precise roles of the different proteins that execute polarity are still poorly understood. Here, we have studied the expression and location of Scribble, the core member of the polarity basal protein complex in epithelial-derived cells, in human and mouse RPE cells in both control and pathological conditions. We found that Scribble specifically localizes at the basolateral membrane of mouse and human RPE cells. In addition, we observed an increase in the expression of Scribble during human RPE development in culture, while it acquires a well-defined basolateral pattern as this process is completed. Finally, the expression and location of Scribble were analyzed in human RPE cells in experimental conditions that mimic the toxic environment suffered by these cells during AMD development and found an increase in Scribble expression in cells that develop a pathological phenotype, suggesting that the protein could be altered in cells under stress conditions, as occurs in AMD. Together, our results demonstrate, for the first time, that Scribble is expressed in both human and mouse RPE and is localized at the basolateral membrane in mature cells. Furthermore, Scribble shows impaired expression and location in RPE cells in pathological conditions, suggesting a possible role for this protein in the development of pathologies, such as AMD.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects PI15/01240 and PI18/01536 co-funded by the European Union (to CL) and by grants from Consejería de Sanidad de la Junta de Castilla y León (GRS2334/A/21 and GRS2167/1/2020). AS was supported by a pre-doctoral fellowship from Junta de Castilla y León co-financed by the European Social Fund

CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH BEST’S DISEASE

Best’s Disease is a macular dystrophy characterized by a lipofuscin accumulation on the retinal pigment epithelium. Five stages have been described based on fundus examination, including choroidal neovascularization. We report a case of a 59-years-old male, presented to the ophthalmologic department with visual loss in both eyes. Fundus examination revealed vitelliform lesions in both maculas. Fluorescein angiography showed a choroidal neovascularization in the left eye. The electrooculogram confirmed the diagnosis of Best's disease. Choroidal neovascularization is a rare complication of Best’s Disease in late stages. The most effective therapeutic options are photodynamic therapy with veteporfirin and antiangiogenic therapy

Acortamiento de la longitud telomérica en adultos jóvenes con catarata

[EN]: [Purpose]: A prospective observational study was performed that included 205 adults, 102 cases and 103 controls, classified into the age groups of ≤ 55 and ≥ 60 years old, to examine the prognostic value of telomere length in patients with or without cataract, and to assess the effects of telomerase ribonucleic acid (RNA) gene variants (TERC and TERT) on telomere length. [Methods]: Telomere length and telomerase polymorphisms were quantified in peripheral blood leukocytes by quantitative polymerase chain reaction. TaqMan® probes were used for telomerase polymorphisms (TERT 1327C>T and TERC 63G>A) genotyping. [Results]: Regardless of age, patients with cataract had shorter telomere lengths compared to healthy controls (p A in both cases and controls, and no correlation was observed between leukocyte telomere length and cardiovascular risk factors in patients with cataracts. [Conclusions]: Irrespective of age, telomeres in peripheral blood leukocytes of patients with cataract were shorter compared to subjects without cataract. Our findings suggest that the development of cataract is associated with peripheral blood cell aging.[ES]: Objetivo]: Se realizo un estudio prospectivo observacional con 205 adultos (102 casos y 103 controles) clasificados en grupos de ≤ 55 anos y ≥ 60 anos, con el fin de evaluar la longitud telomerica en pacientes con y sin catarata, y los efectos de los polimorfismos (TERC y TERT) de la telomerasa sobre dicha longitud. [Métodos]: La longitud telomérica y los polimorfismos de la telomerasa se cuantificaron en leucocitos de sangre periférica por reacción en cadena de la polimerasa. Se utilizaron sondas TaqMan® para genotipificar polimorfismos de telomerasa (TERT 1327C>T y TERC 63G>A). [Resultados]: Independientemente de la edad, los pacientes con catarata tenían longitudes teloméricas más cortas que los controles (p A en casos ni en controles, y no hubo correlación entre la longitud telomérica en los leucocitos y los factores de riesgo cardiovascular en los pacientes con catarata. [Conclusiones]: Sin que influyera la edad, los telómeros en leucocitos de sangre periférica de pacientes con catarata fueron más cortos que en aquellos sin catarata. Nuestros hallazgos sugieren que el desarrollo de cataratas está asociado con el envejecimiento de las células de la sangre periférica.Programa de investigación en salud del Instituto de Salud Carlos III (PI13/01741) cofinanciado con fondos FEDER

Investigation of association between autophagy-related gene polymorphisms and pseudoexfoliation syndrome and pseudoexfoliation glaucoma in a Spanish population

[Purpose]: Cellular stress conditions are important mechanisms implicated in the pathogenesis of pseudoexfoliation syndrome. One of the potential cellular responses to these stress conditions is induction of autophagy. The purpose of this study was to evaluate whether genetic variants in three critical genes of autophagy (ATG16L, ATG2B, ATG5) may be involved in the development of pseudoexfoliation syndrome (XFS) and pseudoexfoliation glaucoma (XFG) in a Spanish population. [Methods]: 108 patients (64 XFS, 44XFG) and 118 healthy controls were evaluated. The analysis of genetic polymorphisms was performed by standard TaqMan allelic discrimination technique. [Results]: No significant differences in either genotype distributions or allelic frequencies of the tested polymorphisms were found between patients with XFS/XFG and control subjects. [Conclusions]: Our results suggest that these three genes that are critical components of the autophagy pathway (ATG16L, ATG2B, ATG5) are not significant risk factors among Spanish patients with either XFS or XFG.Peer Reviewe

Data_Sheet_1_Scribble basal polarity acquisition in RPE cells and its mislocalization in a pathological AMD-like model.PDF

Apicobasal polarity is a hallmark of retinal pigment epithelium cells and is required to perform their functions; however, the precise roles of the different proteins that execute polarity are still poorly understood. Here, we have studied the expression and location of Scribble, the core member of the polarity basal protein complex in epithelial-derived cells, in human and mouse RPE cells in both control and pathological conditions. We found that Scribble specifically localizes at the basolateral membrane of mouse and human RPE cells. In addition, we observed an increase in the expression of Scribble during human RPE development in culture, while it acquires a well-defined basolateral pattern as this process is completed. Finally, the expression and location of Scribble were analyzed in human RPE cells in experimental conditions that mimic the toxic environment suffered by these cells during AMD development and found an increase in Scribble expression in cells that develop a pathological phenotype, suggesting that the protein could be altered in cells under stress conditions, as occurs in AMD. Together, our results demonstrate, for the first time, that Scribble is expressed in both human and mouse RPE and is localized at the basolateral membrane in mature cells. Furthermore, Scribble shows impaired expression and location in RPE cells in pathological conditions, suggesting a possible role for this protein in the development of pathologies, such as AMD.</p

Educación inclusiva en Medicina: una experiencia formativa sobre personas con discapacidad

Resumen: Fundamento: La educación inclusiva universitaria trata de transformar y mejorar el rol competencial de los futuros médicos en relación con las personas con discapacidad (PcD), grupo poblacional vulnerable y prevalente que necesita una atención de calidad para hacer efectivo su derecho a la salud. Objetivo: Analizar y valorar la sensibilización y la formación de una experiencia desarrollada en Medicina en relación con la atención integral a las PcD. Método: Se ha realizado un estudio de intervención, tipo antes y después, sin grupo control, en 120 alumnos del grado de Medicina. Resultados: Los estudiantes perciben que falta de formación en este tema y son conscientes de su rol sanitario y social en la reducción de desigualdades en las PcD. Entre los conocimientos profesionales que mejoran con la intervención, de manera significativa, están los relacionados con los derechos de las PcD, los factores de riesgo, el grado de discapacidad, el diseño universal, las medidas de acción positiva y las adaptaciones curriculares asociadas a la educación inclusiva. En relación con las competencias que deben ser adquiridas, se debe destacar su sensibilización sobre la necesidad de habilidades sociales y de comunicación, y la capacidad para emitir informes médicos sobre la incapacitación. Conclusión: La intervención formativa se muestra efectiva en relación con la sensibilización sobre la importancia del rol del médico en relación con los pacientes con discapacidad y, en consecuencia, se valoran los conocimientos y competencias necesarias para conseguir una mejor atención sanitaria. Abstract: Background: Inclusive higher education aims to transform and improve the competence role of the future doctors in relation to people with disabilities (PwD), a vulnerable and prevalent population group which needs Quality Care to fulfil the right to health. Aim: To analyse and assess the awareness and training received of an experience developed in the School of Medicine related to the comprehensive care for PwD. Method: A before- and after-intervention, with no control group, of 120 students enrolled in the School of Medicine. Results: Students perceive a lack of training on this topic and are aware of their health and social role to reduce inequalities in PwD. The professional knowledge that significantly improved with the intervention are the related with the rights of PwD, risk factors, degree of disability, universal design, positive action measures, and curriculum adaptations. As regards to the competences that must be acquired, the awareness of social and communications skills needed should be noted, as well as the ability to issue medical reports about disability. Conclusion: The training intervention is effective in terms of awareness about the importance of the medical role related to PwD, and consequently, the knowledge and skills needed to achieve a better Health Care are assessed. Palabras clave: Educación inclusiva, Personas con discapacidad, Estudio de intervención, Grado de Medicina, Keywords: Inclusive education, People with disabilities, Intervention study, School of Medicin