Visual Side Effects Linked to Sildenafil Consumption: An Update

Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician’s direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes

Biomarkers for Alzheimer’s Disease Early Diagnosis

Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia

Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration

Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II+ cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat’s life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies.This work was supported by grants from the Spanish Ministry of the Economy and Competitiveness-FEDER (BFU2012-36845, BFU2015-67139-R), Instituto de Salud Carlos III (RETICS-FEDER RD12/0034/0010), Organización Nacional de Ciegos Españoles (ONCE), Asociación Retina Asturias, FUNDALUCE and Fundación Jesús de Gangoiti Barrera

Muerte neural temprana: un proceso inadvertido en el desarrollo del sistema nervioso.

15 p.-7 fig.[EN]During the development of the vertebrate nervous system, multiple physiological processes are involved in the generation of its complex cytoarchitecture and functionality. Among them, programmed cell death has been recognized as a key process that affects connecting neurons. By contrast, there is limited information available regarding the cell death that affects neuroepithelial cells, and recently born neurons and glia, hindering the comprehensive understanding of neural development. We have demonstrated that exquisitely regulated PCD occurs during early stages of neural development such as neurulation and neurogenesis. We have characterized how survival signals from proteins like proinsulin/insulin, c-Raf, and HSC70 counteract caspase-dependent apoptosis, which affects neuroepithelial cells proliferation and the generation of retinal ganglion cells. Furthermore, the characterization of these physiological signals during retinal neurogenesis has the potential to provide new therapeutic tools to attenuate retinal neurodegeneration.[ES]Durante el desarrollo del sistema nervioso de vertebrados, múltiples procesos fisiológicos participan en la generación de su compleja arquitectura celular y funcionalidad. Entre ellos, la muerte celular programada que afecta a neuronas de conexión está reconocido como un proceso fundamental. Por otro lado, hay escasa información disponible acerca de la muerte celular que afecta a células neuroepiteliales y a neuronas y glía recién nacidas, lo que impide que tengamos una noción completa sobre el desarrollo neural. Los estudios de nuestro laboratorio han demostrado que la muerte celular programada se encuentra finamente regulada y ocurre en etapas tan tempranas del desarrollo como la neurulación o la neurogénesis. Hemos caracterizado el papel que moléculas de supervivencia, como la proinsulina/insulina, c-Raf o HSC70, desempeñan bloqueando la apoptosis dependiente de caspasas, proceso que afecta a células neuroepiteliales proliferativas, así como a la generación de las células ganglionares de la retina. Es más, la caracterización de estas señales fisiológicas originadas durante la neurogénesis de la retina nos ha proporcionado una nueva herramienta terapéutica potencial para el tratamiento y atenuación de las neurodegeneraciones retinianas.Research in the laboratory is funded by grants-in-aid from the Spanish Ministerio de Educación y Ciencia (SAF2007-66175-C02-01 to EJdlR, BFU2007-61055/BMC to FdP, and BFU2006-00508 to PB).Peer reviewe

Relationship of Limb Lengths and Body Composition to Lifting in Weightlifting

Weightlifting is a discipline where technique and anthropometric characteristics are essential to achieve the best results in competitions. This study aims to analyse the relationships between body composition, limb length and barbell kinematics in the performance of weightlifters. It consists of an observational and descriptive study of 19 athletes (12 men [28.50 ± 6.37 years old; 84.58 ± 14.11 kg; 176.18 ± 6.85 cm] and 7 women [27.71 ± 6.34 years old; 64.41 ± 7.63 kg; 166.94 ± 4.11 cm]) who met the inclusion criteria. A level I anthropometrist took anthropometric measures according to the methodology of the International Society for the Advancement of Kinanthropometry (ISAK), and the measurement of the barbell velocity was made with the software Kinovea. In terms of body composition, both genders are within the percentage range of fat mass recommended for this sport. In female weightlifters, there is a positive correlation between foot length, maximal velocity in the Snatch (ρ = 0.775, p = 0.041), and performance indicator in the Snatch and the Clean & Jerk (ρ = 0.964, p < 0.001; ρ = 0.883, p = 0.008, respectively). In male weightlifters, a positive correlation between tibial length and average velocity of the barbell in the Snatch is observed (ρ = 0.848, p < 0.001). Muscle mass percentage correlates positively with performance indicator in both techniques (ρ = 0.634, p = 0.027; ρ = 0.720, p = 0.008). Also, the relative length of the upper limb is negatively correlated with the performance indicator (ρ = −0.602, p = 0.038). Anthropometry and body composition may facilitate skill acquisition among this sport population, contributing to increase the limited body of scientific knowledge related to weightlifting

Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.This work was supported by project grants from Spanish Ministerio de Economía y Competitividad-FEDER (http://www.mineco.gob.es) #BFU2012‐36845, Instituto de Salud Carlos III RETICS (http://www.oftared.com) #RD12/0034/0010 and Organización Nacional de Ciegos Españoles (http://www.once.es) to NC; Ministerio de Ciencia e Innovación #JCI‐2009‐05224 to VGV; Universidad de Alicante (http://www.ua.es) #2010-48536273 to GE; Instituto de Salud Carlos III (http://www.isciii.es) #PI13/02098 and RETICS #RD12/0034/0006 to PdV; and FUNDALUCE

Deleterious Effect of NMDA Plus Kainate on the Inner Retinal Cells and Ganglion Cell Projection of the Mouse

Combined administration of N-Methyl-D-Aspartate (NMDA) and kainic acid (KA) on the inner retina was studied as a model of excitotoxicity. The right eye of C57BL6J mice was injected with 1 µL of PBS containing NMDA 30 mM and KA 10 mM. Only PBS was injected in the left eye. One week after intraocular injection, electroretinogram recordings and immunohistochemistry were performed on both eyes. Retinal ganglion cell (RGC) projections were studied by fluorescent-cholerotoxin anterograde labeling. A clear decrease of the retinal “b” wave amplitude, both in scotopic and photopic conditions, was observed in the eyes injected with NMDA/KA. No significant effect on the “a” wave amplitude was observed, indicating the preservation of photoreceptors. Immunocytochemical labeling showed no effects on the outer nuclear layer, but a significant thinning on the inner retinal layers, thus indicating that NMDA and KA induce a deleterious effect on bipolar, amacrine and ganglion cells. Anterograde tracing of the visual pathway after NMDA and KA injection showed the absence of RGC projections to the contralateral superior colliculus and lateral geniculate nucleus. We conclude that glutamate receptor agonists, NMDA and KA, induce a deleterious effect of the inner retina when injected together into the vitreous chamber.This research was funded by the Instituto de Salud Carlos III and co‐funded by the European Regional Development Fund (ERDF) within the “Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020” (grant numbers #RD16/0008/0016; #RD16/0008/0020; #FIS/PI 18‐00754)

Ensayo de evaluación a distancia frente a evaluación presencial

El sistema de evaluación debe valorar las competencias adquiridas por el estudiante según los conocimientos, habilidades y aptitudes que ha desarrollado a lo largo del proceso de enseñanza-aprendizaje. Este proceso debe ser válido, además de confiable y práctico. Es necesario estudiar los diversos métodos de evaluación disponibles y su idoneidad para las distintas actividades de los grados. El hecho de disponer de herramientas que permiten realizar una evaluación a distancia nos hizo plantearnos la idoneidad de este sistema. Así pues, con el objeto de evaluar la fiabilidad de la evaluación a distancia, se realizó una experiencia en la que se compararon las calificaciones obtenidas en actividades prácticas y seminarios, empleando ambas modalidades de evaluación: presencial y a distancia, mediante las herramientas del campus virtual. Como pudimos comprobar, no hubo diferencias significativas según la modalidad de evaluación, por lo que, con los datos de los que disponemos, podemos aceptar ambos sistemas como igualmente efectivos. Estudiamos también el efecto de la realización de una prueba previa de autoevaluación. En este caso sí encontramos como consecuencia un ligero incremento en la nota, por lo que recomendamos esta actividad para la mejora del rendimiento académico

Immunosuppression, peripheral inflammation and invasive infection from endogenous gut microbiota activate retinal microglia in mouse models

Although its actual role in the progression of degenerative processes is not fully known, the persistent activated state of retinal microglia and the concurrent secretion of inflammatory mediators may contribute to neuronal death and permanent vision loss. Our objective was to determine whether non-ocular conditions (immunosuppression and peripheral inflammation) could lead to activation of retinal microglia. Mouse models of immunosuppression induced by cyclophosphamide and/or peripheral inflammation by chemically induced sublethal colitis in C57BL/6J mice were used. Retinal microglia morphology, spatial distribution and complexity, as well as MHCII and CD11b expression levels were determined by flow cytometry and confocal immunofluorescence analysis with anti-CD11b, anti-IBA1 and anti-MHCIIRT1B antibodies. Retinas of mice with double treatment showed changes in microglial morphology, spatial distribution and expression levels of CD11b and MHCII. These effects were higher than those observed with any treatment separately. In addition, we also observed in these mice: (i) translocation of endogenous bacteria from gut to liver, and (ii) upregulation of TLR2 expression in retinal microglia. Using a mouse model of immunosuppression and gut colonization by Candida albicans, translocation of fungal cells was confirmed to occur in wild type and, to a higher extent, in TLR2 KO mice, which are more susceptible to fungal invasion; interestingly microglial changes were also higher in TLR2 KO mice. Hence, non-ocular injuries (immunosuppression, peripheral inflammation and invasive infection from endogenous gut microbiota) can activate retinal microglia and therefore could affect the progression of neurodegenerative disorders and should be taken into account to improve therapeutic options.This study was supported by project grants from the Spanish Ministry of Economy and Competitiveness-FEDER BFU2012-36845, Instituto de Salud Carlos III RETICS RD12/0034/0010, FUNDALUCE, Retina Asturias, ONCE and Fundación Jesús de Gangoiti Barrera

Rendimiento académico del ABP en Anatomía

Desde que en la Universidad de Alicante se implantaron los nuevos planes de estudios EEES en el curso 2010-11, hasta la actualidad, se ha estado aplicando la metodología docente colaborativa de aprendizaje basado en problemas (ABP) en asignaturas del área de Anatomía Humana y Embriología impartidas en los primeros cursos de las titulaciones de Grado en “Enfermería”, “Nutrición Humana y Dietética”, “Óptica y Optometría” y “Ciencias de la Actividad Física y del Deporte”. El objetivo de este estudio es comparar los resultados de aprendizaje a través del rendimiento académico obtenido en la evaluación continua según diferentes metodologías docentes. En general, las calificaciones obtenidas en la evaluación de la exposición oral en grupo del trabajo ABP fueron mucho mejores en todas las asignaturas a lo largo de los últimos 5 años. Los resultados de las pruebas objetivas de respuesta múltiple usadas para evaluar los logros de aprendizaje mediante el uso de clases magistrales de teoría y prácticas de laboratorio fueron algo inferiores. Se plantea la posibilidad de incrementar el número de actividades de ABP y asignar un mayor peso en la ponderación de los criterios de evaluación de la asignatura