Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi−) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

Partial rescue of retinal function in chronically hypoglycemic mice

Purpose. Mice rendered hypoglycemic by a null mutation in the glucagon receptor gene Gcgr display late-onset retinal degeneration and loss of retinal sensitivity. Acute hyperglycemia induced by dextrose ingestion does not restore their retinal function, which is consistent with irreversible loss of vision. The goal of this study was to establish whether long-term administration of high dietary glucose rescues retinal function and circuit connectivity in aged Gcgr−/− mice. Methods. Gcgr−/− mice were administered a carbohydrate-rich diet starting at 12 months of age. After 1 month of treatment, retinal function and structure were evaluated using electroretinographic (ERG) recordings and immunohistochemistry. Results. Treatment with a carbohydrate-rich diet raised blood glucose levels and improved retinal function in Gcgr−/− mice. Blood glucose increased from moderate hypoglycemia to euglycemic levels, whereas ERG b-wave sensitivity improved approximately 10-fold. Because the b-wave reflects the electrical activity of second-order cells, we examined for changes in rod-to-bipolar cell synapses. Gcgr−/− retinas have 20% fewer synaptic pairings than Gcgr+/− retinas. Remarkably, most of the lost synapses were located farthest from the bipolar cell body, near the distal boundary of the outer plexiform layer (OPL), suggesting that apical synapses are most vulnerable to chronic hypoglycemia. Although treatment with the carbohydrate-rich diet restored retinal function, it did not restore these synaptic contacts. Conclusions. Prolonged exposure to diet-induced euglycemia improves retinal function but does not reestablish synaptic contacts lost by chronic hypoglycemia. These results suggest that retinal neurons have a homeostatic mechanism that integrates energetic status over prolonged periods of time and allows them to recover functionality despite synaptic loss.

Rotenone induces degeneration of photoreceptors and impairs the dopaminergic system in the rat retina

Rotenone is a widely used pesticide and a potent inhibitor of mitochondrial complex I (NADH-quinone reductase) that elicits the degeneration of dopaminergic neurons and thereby the appearance of a parkinsonian syndrome. Here we have addressed the alterations induced by rotenone at the functional, morphological and molecular levels in the retina, including those involving both dopaminergic and non-dopaminergic retinal neurons. Rotenone-treated rats showed abnormalities in equilibrium, postural instability and involuntary movements. In their outer retina we observed a loss of photoreceptors, and a reduced synaptic connectivity between those remaining and their postsynaptic neurons. A dramatic loss of mitochondria was observed in the inner segments, as well as in the axon terminals of photoreceptors. In the inner retina we observed a decrease in the expression of dopaminergic cell molecular markers, including loss of tyrosine hydroxylase immunoreactivity, associated with a reduction of the dopaminergic plexus and cell bodies. An increase in immunoreactivity of AII amacrine cells for parvalbumin, a Ca2+-scavenging protein, was also detected. These abnormalities were accompanied by a decrease in the amplitude of scotopic and photopic a- and b-waves and an increase in the b-wave implicit time, as well as by a lower amplitude and greater latency in oscillatory potentials. These results indicate that rotenone induces loss of vision by promoting photoreceptor cell death and impairment of the dopaminergic retinal system.

Reducing visual deficits caused by refractive errors in school and preschool children: results of a pilot school program in the Andean region of Apurimac, Peru

Background: Refractive error is defined as the inability of the eye to bring parallel rays of light into focus on the retina, resulting in nearsightedness (myopia), farsightedness (Hyperopia) or astigmatism. Uncorrected refractive error in children is associated with increased morbidity and reduced educational opportunities. Vision screening (VS) is a method for identifying children with visual impairment or eye conditions likely to lead to visual impairment. Objective: To analyze the utility of vision screening conducted by teachers and to contribute to a better estimation of the prevalence of childhood refractive errors in Apurimac, Peru. Design: A pilot vision screening program in preschool (Group I) and elementary school children (Group II) was conducted with the participation of 26 trained teachers. Children whose visual acuity was<6/9 [20/30] (Group I) and≤6/9 (Group II) in one or both eyes, measured with the Snellen Tumbling E chart at 6 m, were referred for a comprehensive eye exam. Specificity and positive predictive value to detect refractive error were calculated against clinical examination. Program assessment with participants was conducted to evaluate outcomes and procedures. Results: A total sample of 364 children aged 3–11 were screened; 45 children were examined at Centro Oftalmológico Monseñor Enrique Pelach (COMEP) Eye Hospital. Prevalence of refractive error was 6.2% (Group I) and 6.9% (Group II); specificity of teacher vision screening was 95.8% and 93.0%, while positive predictive value was 59.1% and 47.8% for each group, respectively. Aspects highlighted to improve the program included extending training, increasing parental involvement, and helping referred children to attend the hospital. Conclusion: Prevalence of refractive error in children is significant in the region. Vision screening performed by trained teachers is a valid intervention for early detection of refractive error, including screening of preschool children. Program sustainability and improvements in education and quality of life resulting from childhood vision screening require further research.

Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration

Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant retinitis pigmentosa (RP). In P23H rats administered with HU210 (100 μg/kg, i.p.) from P24 to P90, ERG recordings showed an amelioration of vision loss, as compared to vehicle-administered animals. Under scotopic conditions, the maximum a-wave amplitudes recorded at P60 and P90 were higher in HU210-treated animals, as compared to the values obtained in untreated animals. The scotopic b-waves were significantly higher in treated animals than in untreated rats at P30, P60 and P90. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. HU210-treated animals had 40% more photoreceptors than untreated animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were also preserved in HU210-treated P23H rats. These results indicate that HU210 preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in P23H rats. These data suggest that cannabinoids are potentially useful to delay retinal degeneration in RP patients.

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.

New hybrid materials based on the grafting of Pd(II)-amino complexes on the graphitic surface of AC: preparation, structures and catalytic properties

A novel procedure for the preparation of solid Pd(II)-based catalysts consisting of the anchorage of designed Pd(II)-complexes on an activated carbon (AC) surface is reported. Two molecules of the Ar–S–F type (where Ar is a plane-pyrimidine moiety, F a Pd(II)-ligand and S an aliphatic linker) differing in F, were grafted on AC by π–π stacking of the Ar moiety and the graphene planes of the AC, thus favouring the retaining of the metal-complexing ability of F. Adsorption of Pd(II) by the AC/Ar–S–F hybrids occurs via Pd(II)-complexation by F. After deep characterization, the catalytic activities of the AC/Ar–S–F/Pd(II) hybrids on the hydrogenation of 1-octene in methanol as a catalytic test were evaluated. 100% conversion to n-octane at T = 323.1 K and P = 15 bar, was obtained with both catalysts and most of Pd(II) was reduced to Pd(0) nanoparticles, which remained on the AC surface. Reusing the catalysts in three additional cycles reveals that the catalyst bearing the F ligand with a larger Pd-complexing ability showed no loss of activity (100% conversion to n-octane) which is assigned to its larger structural stability. The catalyst with the weaker F ligand underwent a progressive loss of activity (from 100% to 79% in four cycles), due to the constant aggregation of the Pd(0) nanoparticles. Milder conditions, T = 303.1 K and P = 1.5 bar, prevent the aggregation of the Pd(0) nanoparticles in this catalyst allowing the retention of the high catalytic efficiency (100% conversion) in four reaction cycles.

Las maquetas como material didáctico para la enseñanza y aprendizaje de la lectura e interpretación de planos en la ingeniería

Utilizamos las maquetas como herramientas auxiliares para proyectar y mostrar proyectos de ingeniería, pero también pueden ser un excelente material didáctico para la enseñanza y aprendizaje de la lectura, interpretación y realización de los planos que definen un proyecto o sus diferentes elementos. En este trabajo se refiere la experiencia realizada por los autores con los alumnos de Ingeniería Técnica de Obras Públicas dentro de la unidad de Interpretación de Planos de la asignatura de Sistemas de Representación. La dificultad que los alumnos de la materia tienen para interpretar el lenguaje, códigos y convenciones de la expresión gráfica está entre los motivos por los que se ha utilizado las maquetas como método de representación tridimensional que permite hacer comprensibles y fácilmente interpretadas las características constructivas de los diferentes elementos y las operaciones necesarias para pasar de la representación a la realización de la unidad de obra. En la comunicación se describe la actividad realizada con los alumnos, la selección de las unidades a representar, la elaboración de las maquetas y planos, poniendo especial acento en la concordancia entre la representación gráfica y el modelo tridimensional. Asimismo se han analizado las capacidades didácticas de uno de los trabajos realizados por los alumnos así como la evaluación y conclusiones de la experiencia realizada.

Dibujando la arquitectura olvidada: las defensas militares de la guerra de 1936-39 [PPT]

A decade before there was getting up the 'Atlantic Wall', there was executed a system of defenses along the Mediterranean coast in Spain (1936-39). The recovery of the same constructions (both of his graphical documents and of the constructed works that stay in foot) and his putting in value it can help to consolidate an own memory of the 20th century. This work considers to inventory, to measure and to draw the planes of these architectures to fix the memory that is diluted by the erosion of the time. The military pieces place in many borders: are these properly architecture? These are walking between two epochs: the one that perpetuates the epic acts in opposite to the one that shows the disasters in order that they do not forget. They are the most modern ruins of our history. In this process of reconstruction of the memory, there turns out to be crucial the graphical restitution. The drawing is a source of knowledge and demonstrates facts that were constructed.

Dibujando la arquitectura olvidada: las defensas militares de la guerra de 1936-39

Comunicación presentada en el XI Congreso Internacional de Expresión Gráfica Aplicada a la Edificación, APEGA 2012, Valencia, 29 noviemnre-1 diciembre 2012.

Retinal image quality assessment through a visual similarity index

Retinal image quality is commonly analyzed through parameters inherited from instrumental optics. These parameters are defined for ‘good optics’ so they are hard to translate into visual quality metrics. Instead of using point or artificial functions, we propose a quality index that takes into account properties of natural images. These images usually show strong local correlations that help to interpret the image. Our aim is to derive an objective index that quantifies the quality of vision by taking into account the local structure of the scene, instead of focusing on a particular aberration. As we show, this index highly correlates with visual acuity and allows inter-comparison of natural images around the retina. The usefulness of the index is proven through the analysis of real eyes before and after undergoing corneal surgery, which usually are hard to analyze with standard metrics.

Muro Mediterráneo versus movimiento moderno

Una década antes de que fuera construido el Muro Atlántico fue ejecutado un sistema de defensas a lo largo de la costa del Mediterráneo español (1936-39). La recuperación de estas construcciones (de sus documentos gráficos) y su puesta en valor pueden ayudar a consolidar una memoria propia del siglo XX. Este trabajo consiste en inventariar, medir y dibujar los planos de estas arquitecturas a fin de fijar la memoria que se diluye por la erosión del tiempo. Estas defensas militares se sitúan en muchas fronteras: ¿son propiamente arquitectura o piezas industriales? ¿Son arquitectura moderna? Estas transitan entre dos mundos: uno que proyecta arquitecturas ligeras, flexibles y con caducidad frente a otro que construye obras compactas, rígidas y eternas. También se mueven por dos épocas: una que perpetúa las hazañas épicas frente a otras que muestra los desastres. Espacio, tiempo y materia. Son las ruinas de hormigón más modernas de nuestra historia que se encuentran camufladas en la topografía: templos y tumbas a la vez. En esta reconstrucción de la memoria, resulta crucial la restitución gráfica que es donde comienza el conocimiento.

A new approach for semi-automatic rock mass joints recognition from 3D point clouds

Rock mass characterization requires a deep geometric understanding of the discontinuity sets affecting rock exposures. Recent advances in Light Detection and Ranging (LiDAR) instrumentation currently allow quick and accurate 3D data acquisition, yielding on the development of new methodologies for the automatic characterization of rock mass discontinuities. This paper presents a methodology for the identification and analysis of flat surfaces outcropping in a rocky slope using the 3D data obtained with LiDAR. This method identifies and defines the algebraic equations of the different planes of the rock slope surface by applying an analysis based on a neighbouring points coplanarity test, finding principal orientations by Kernel Density Estimation and identifying clusters by the Density-Based Scan Algorithm with Noise. Different sources of information —synthetic and 3D scanned data— were employed, performing a complete sensitivity analysis of the parameters in order to identify the optimal value of the variables of the proposed method. In addition, raw source files and obtained results are freely provided in order to allow to a more straightforward method comparison aiming to a more reproducible research.

Análisis de la eficacia de la terapia visual en el tratamiento de la exotropía intermitente mediante videooculografía 3D

Objetivo: Evaluar la eficacia del tratamiento en 3 casos de exotropia intermitente (XT(i)) mediante ejercicios de terapia visual, completando la exploración clínica con Videooculografia-30 y evidenciar la potencial aplicabilidad de esta tecnología para dicho propósito. Métodos: Exponemos los cambios ocurridos tras ejercicios de terapia visual en una mujer de 36 años con XT(i) de -25 dioptrías prismáticas (dp) de lejos y 18 dp de cerca; Un niño de 10 años de edad con 8 dp de XT(i) en posición primaria, asociados a +6 dp de hipotropia izquierda; y un hombre de 63 años con XT(i) de 6 dp en posición primaria asociada a +7 dp de hipertropia derecha. Todos los pacientes presentaron buena agudeza visual corregida en ambos ojos. La inestabilidad de la desviación ocular se evidenció mediante análisis de VOG-30, revelando la presencia de components verticales y torsionales. Se realizaron ejercicios de terapia visual, incluyendo diferentes tipos de ejercicios de vergencias, acomodación y percepción de la diplopía. Resultados: Tras la terapia visual se obtuvieron excelentes rangos de vergencias fusionales y de punto próximo de convergencia («hasta la nariz»). El examen mediante VOG-3D (Sensoro Motoric lnstruments, Teltow, Germany) confirmó la compensación de la desviación con estabilidad del alineamiento ocular. Se observó una significativa mejora después de la terapia en los components verticals y torsionales, lo cuales se hicieron más estables. Los pacientes se mostraron muy satisfechos de los resultados obtenidos. Conclusión: La VOG-3D es una técnica útil para dotamos de un método objetivo de registro de la compensación y estabilidad de la desviación ocular después de realizar ejercicios de terapia visual en casos de XT(i), ofreciéndonos un detallado análisis de la mejoría de los components verticales y torsionales.