Le système endocannabinoïde dans la rétine du singe : expression, localisation et fonctions

Le cannabis produit de nombreux effets psychologiques et physiologiques sur le corps humain. Les molécules contenues dans cette plante, désignées comme « phytocannabinoïdes », activent un système endogène qu’on appelle le système endocannabinoïde (eCB). Les effets de la consommation de cannabis sur la vision ont déjà été décrits sans cependant de formulation sur les mécanismes sous-jacents. Ces résultats comportementaux suggèrent, malgré tout, la présence de ce système eCB dans le système visuel, et particulièrement dans la rétine. Cette thèse vise donc à caractériser l’expression, la localisation et le rôle du système eCB dans la rétine du singe vervet, une espèce animale ayant un système visuel semblable à celui de l’humain. Nous avons mis au point un protocole expérimental d’immunohistochimie décrit dans l’article apparaissant dans l’Annexe I que nous avons utilisé pour répondre à notre objectif principal. Dans une première série de quatre articles, nous avons ainsi caractérisé l’expression et la localisation de deux récepteurs eCBs reconnus, les récepteurs cannabinoïdes de type 1 (CB1R) et de type 2 (CB2R), et d’un 3e présumé récepteur aux cannabinoïdes, le récepteur GPR55. Dans l’article 1, nous avons démontré que CB1R et une enzyme clé de ce système, la fatty acid amide hydrolase (FAAH), sont exprimés dans les parties centrale et périphérique de la rétine, et abondamment présents dans la fovéa, une région où l’acuité visuelle est maximale. Dans l’article 2, nous avons localisé le CB2R dans des cellules gliales de la rétine : les cellules de Müller et nous avons proposé un modèle sur l’action de cette protéine dans la fonction rétinienne faisant appel à une cascade chimique impliquant les canaux potassiques. Dans l’article 3, nous avons observé le GPR55 exclusivement dans les bâtonnets qui sont responsables de la vision scotopique et nous avons soumis un deuxième modèle de fonctionnement de ce récepteur par le biais d'une modulation des canaux calciques et sodiques des bâtonnets. Vu que ces 3 récepteurs se retrouvent dans des cellules distinctes, nous avons suggéré leur rôle primordial dans l’analyse de l’information visuelle au niveau rétinien. Dans l’article 4, nous avons effectué une analyse comparative de l’expression du système eCB dans la rétine de souris, de toupayes (petits mammifères insectivores qui sont sont considérés comme l’étape intermédiaire entre les rongeurs et les primates) et de deux espèces de singe (le vervet et le rhésus). Ces résultats nous ont menés à présenter une hypothèse évolutionniste quant à l’apparition et à la fonction précise de ces récepteurs. Dans les articles subséquents, nous avons confirmé notre hypothèse sur le rôle spécifique de ces trois récepteurs par l’utilisation de l’électrorétinographie (ERG) après injection intravitréenne d’agonistes et d’antagonistes de ces récepteurs. Nous avons conclu sur leur influence indéniable dans le processus visuel rétinien chez le primate. Dans l’article 5, nous avons établi le protocole d’enregistrement ERG normalisé sur le singe vervet, et nous avons produit un atlas d’ondes ERG spécifique à cette espèce, selon les règles de l’International Society for Clinical Electrophysiology of Vision (ISCEV). Les patrons électrorétinographiques se sont avérés semblables à ceux de l’humain et ont confirmé la similarité entre ces deux espèces. Dans l’article 6, nous avons démontré que le blocage de CB1R ou CB2R entraine une modification de l’électrorétinogramme, tant au niveau photopique que scotopique, ce qui supporte l’implication de ces récepteurs dans la modulation des ondes de l’ERG. Finalement, dans l’article 7, nous avons confirmé le modèle neurochimique proposé dans l’article 3 pour expliquer le rôle fonctionnel de GPR55, en montrant que l’activation ou le blocage de ce récepteur, respectivement par un agoniste (lysophosphatidylglucoside, LPG) ou un antagoniste (CID16020046), entraine soit une augmentation ou une baisse significative de l’ERG scotopique seulement. Ces données, prises ensemble, démontrent que les récepteurs CB1R, CB2R et GPR55 sont exprimés dans des types cellulaires bien distincts de la rétine du singe et ont chacun un rôle spécifique. L’importance de notre travail se manifeste aussi par des applications cliniques en permettant le développement de cibles pharmacologiques potentielles dans le traitement des maladies de la rétine.

South-West Monsoon Rainfall of Kerala and Its Variability

This study focuses on the south –west monsoon rainfall over Kerala and its variability both on the spatial and temporal scales. The main objectives of the study are, interanual, long-term and decadal variabilities in MRF(monsoon rain fall),relationship between antecedent global circulation parameters, diurnal variability using data of a large number of stations in Kerala and the spatial distribution of rainfall under two large scale synoptic. Kerala gets nearly 190cm of rainfall during the south-west monsoon season 1st June to 30th September. This is more than twice the monsoon rainfall of India. A good part of kerala’s rainfall is caused by the orography of the Western Ghats Mountain ranges. The state receives 286cm of annual rainfall of which 68%is during the south-west monsoon season. The summer monsoon rainfall of Kerala shows a decreasing trend of 12.0%in 96 years. The study shows that the Intra Seasonal Oscillations(ISO) of the monsoon season has large interanual variability,some years having long period and other years having short period ISO. It is seen that Western Ghats has a strong control on the east west profile on the monsoon rainfall.

Studies on the Vertical Structure of Horizontal Wind Variability in the Surface Boundary Layer Over Sriharikota

The present study on the vertical structure of horizontal wind variability in the surface boundary layer over Sriharikota. Based on clock wind speed and direction measuring meteorological tower facility from seven levels in the 100 m layer. The study on wind variability and elliptical approximation of wind hodographs investigated for this tropical coastal station established that Sriharikota is of meso-scale weather entity. Wind variability ratio increases from lower levels to upper levels. In South West monsoon months the station is of high ratio values and it gets affected with meso-scale weather features like thunderstorms. Average total shears are observed greater values than scalar shears. Scalar shears are high in the lowest shear levels compared to upper levels. Semi diurnal types of oscillation in average total shears are found in south west monsoon months. During cyclonic storm passage it is observed that there can be significant difference in mean wind speed from 10 m to 100 m level, but it is not so for peak wind speeds. The variations in wind variability ratio in different months is clearly depicted its strong link to define meso-scale or synoptic –scale forcing domination for this station. Meso-scale forcing is characterized by diurnal wind variability and synoptic- scale forcing by interdiurnal wind variability.

Dynamic characteristics of Atmospheric boundary Layer during different phases of Monsoon

Atmospheric Boundary layer (ABL) is the layer just above the earth surface and is influenced by the surface forcing within a short period of an hour or less. In this thesis, characteristics of the boundary layer over ocean, coastal and inland areas of the atmosphere, especially over the monsoon regime are thoroughly studied. The study of the coastal zone is important due to its high vulnerability mainly due to sea breeze circulation and associated changes in the atmospheric boundary layer. The major scientific problems addressed in this thesis are diurnal and seasonal variation of coastal meteorological properties, the characteristic difference in the ABL during active and weak monsoons, features of ABL over marine environment and the variation of the boundary layer structure over an inland station. The thesis describes the various features in the ABL associated with the active and weak monsoons and, the surface boundary layer properties associated with the active and weak epochs. The study provides knowledge on MABL and can be used as the estimated values of boundary layer parameters over the marine atmosphere and to know the values and variabilities of the ABL parameters such as surface wind, surface friction, drag coefficient, wind stress and wind stress curl.

Studies on rainfall variability and the influence of orography and land use on the climate of Peninsular India

The present study helped to understand the trend in rainfall patterns at smaller spatial scales and the large regional differences in the variability of rainfall. The effect of land use and orography on the diurnal variability is also understood. But a better understanding on the long term variation in rainfall is possible by using a longer dataset,which may provide insight into the rainfall variation over country during the past century. The basic mechanism behind the interannual rainfall variability would be possible with numerical studies using coupled Ocean-Atmosphere models. The regional difference in the active-break conditions points to the significance of regional studies than considering India as a single unit. The underlying dynamics of diurnal variability need to be studied by making use of a high resolution model as the present study could not simulate the local onshore circulation. Also the land use modification in this study, selected a region, which is surrounded by crop land. This implies the high possibility for the conversion of the remaining region to agricultural land. Therefore the study is useful than considering idealized conditions, but the adverse effect of irrigated crop is more than non-irrigated crop. Therefore, such studies would help to understand the climate changes occurred in the recent period. The large accumulation of rainfall between 300-600 m height of western Ghats has been found but the reason behind this need to be studied, which is possible by utilizing datasets that would better represent the orography and landuse over the region in high resolution model. Similarly a detailed analysis is needed to clearly identify the causative relations of the predictors identified with the predictant and the physical reasons behind them. New approaches that include nonlinear relationships and dynamical variables from model simulations can be included in the existing statistical models to improve the skill of the models. Also the statistical models for the forecasts of monsoon have to be continually updated.

Sterols in mangrove sediments of the cochin estuary

The thesis entitled “Sterols in Mangrove Sediments of the Cochin Estuary” is an attempt to characterize the sterol content of the mangrove sediments, their dietary status with respect to the natural flora and fauna present, their transfonnations in the sediment and assess contributions, if any to the nursery character of the mangrove eco system. Samplings were done from two sites at Mangalavanam and Vypin. Mangalavanam is a patchy mangrove area in the heart of the city of Cochin and serves as a small bird sanctuary. This is an almost closed system with a single narrow canal linking to the estuary. Vypin, the largest single stretch of mangroves in Kerala, is regularly inundated by a semi diurnal rhythm of Cochin bar mouth. Perhaps, this is the only site in Kerala where one can see mangroves right along the accreting seacoast. However a lot of developmental pressure is threatening the very existence of these mangroves. Post monsoon sediment samples from these areas were used for the present study, as it is the period of maximum faunal growth and activity

Studies on sporulation and propagation in selected agarophytes

Studies on sporulation of four commercially important red (sea-weeds) algae ^(agarophytes) namely Gelidiella acerosa, Gracilaria corticata, G edulis and Hypnea musciformis growing in the vicinity of’ Mandapam coast were carried out from October 1981 to September 1983. During the two years of study; fruiting behavior in the natural population of these species was also investigated. Laboratory experiments were carried out with the four algae sea weeds to collect information on seasonal aspects of spore production and diurnal variation of spore shedding. Detailed studies were made under laboratory conditions to know the effects of some selected environmental factors such as desiccation, salinity, temperature, light intensity and photoperiod on spore output in Gelidiella acerosa, Gracilaria edulis and kypnea musciformis hydrological data were also collected from the inter-tial region around mandapam area. The result obtained on all the above aspects are presented in this thesis

Thermohaline variability in the upper layers of the Arabian Sea

The Arabian Sea is an area of complex air-sea interaction processes with seasonal reversing monsoons. The associated thermohaline variability in the upper layers appears to control the large scale monsoon flow which is not yet completely understood. The variability in the thermohaline fields is known to occur in temporal domain ranging from intra-diurnal to inter-annual time scales and on spatial domains of few tens of kilometers to few thousands of kilometers. In the Arabian Sea though the surface temperature was routinely measured by both conventional measurements and satellites, the corresponding information on the subsurface thermohaline field is very sparse due to the lack cw adequate measurements. In such cases the numerical models offer promise in providing information on the subsurface features given an initial thermohaline field and surface heat flux boundary conditions. This thesis is an outcome of investigations carried out on the various aspects of the thermohaline variability on different time scales. In addition to the description of the mean annual cycle. the one dimensional numerical models of Miller (1976) and Price et a1 (1986) are utilised to simulate the observed mixed layer characteristics at selected locations in the Arabian Sea on time scales ranging from intra-diurnal to synoptic scales under variable atmospheric forcing.

Spatial and temporal characteristics of rain intensity in the peninsular Malaysia using TRMM rain rate

The present study is focused on the intensity distribution of rainfall in different classes and their contribution to the total seasonal rainfall. In addition, we studied the spatial and diurnal variation of the rainfall in the study areas. For the present study, we retrieved data from TRMM (Tropical Rain Measuring Mission) rain rate available in every 3 h temporal and 25 km spatial resolutions. Moreover, station rainfall data is used to validate the TRMM rain rate and found significant correlation between them (linear correlation coefficients are 0.96, 0.85, 0.75 and 0.63 for the stations Kota Bharu, Senai, Cameron highlands and KLIA, respectively). We selected four areas in the Peninsular Malaysia and they are south coastal, east coastal, west coastal and highland regions. Diurnal variation of frequency of rain occurrence is different for different locations. We noticed bimodal variation in the coastal areas in most of the seasons and unimodal variation in the highland/inland area. During the southwest monsoon period in the west coastal stations, there is no distinct diurnal variation. The distribution of different intensity classes during different seasons are explained in detail in the results

Studies on Copepods from the EEZ of India-Bay of Bengal and Andaman Sea

The main objectives of the study are: To study the seasonal distribution of copepods with special reference to their qualitative and quantitative distribution, with notes on biodiversity in the Andaman Sea and the Bay of Bengal. To study the spatial and temporal distribution of copepods in the Andaman Sea and the Bay of Bengal.To understand the hydrography and the environmental characteristics of the Andaman Sea and the Bay of Bengal and their role in the distribution and biomass of copepods.To study the vertical migration/diurnal migration of the copepods. To study the difference between the coastal and oceanic composition of copepods in the study area and the factors responsible for it.

Stimulus Simplification and Object Representation: A Modeling Study

Tsunoda et al. (2001) recently studied the nature of object representation in monkey inferotemporal cortex using a combination of optical imaging and extracellular recordings. In particular, they examined IT neuron responses to complex natural objects and "simplified" versions thereof. In that study, in 42% of the cases, optical imaging revealed a decrease in the number of activation patches in IT as stimuli were "simplified". However, in 58% of the cases, "simplification" of the stimuli actually led to the appearance of additional activation patches in IT. Based on these results, the authors propose a scheme in which an object is represented by combinations of active and inactive columns coding for individual features. We examine the patterns of activation caused by the same stimuli as used by Tsunoda et al. in our model of object recognition in cortex (Riesenhuber 99). We find that object-tuned units can show a pattern of appearance and disappearance of features identical to the experiment. Thus, the data of Tsunoda et al. appear to be in quantitative agreement with a simple object-based representation in which an object's identity is coded by its similarities to reference objects. Moreover, the agreement of simulations and experiment suggests that the simplification procedure used by Tsunoda (2001) is not necessarily an accurate method to determine neuronal tuning.

Categorization in IT and PFC: Model and Experiments

In a recent experiment, Freedman et al. recorded from inferotemporal (IT) and prefrontal cortices (PFC) of monkeys performing a "cat/dog" categorization task (Freedman 2001 and Freedman, Riesenhuber, Poggio, Miller 2001). In this paper we analyze the tuning properties of view-tuned units in our HMAX model of object recognition in cortex (Riesenhuber 1999) using the same paradigm and stimuli as in the experiment. We then compare the simulation results to the monkey inferotemporal neuron population data. We find that view-tuned model IT units that were trained without any explicit category information can show category-related tuning as observed in the experiment. This suggests that the tuning properties of experimental IT neurons might primarily be shaped by bottom-up stimulus-space statistics, with little influence of top-down task-specific information. The population of experimental PFC neurons, on the other hand, shows tuning properties that cannot be explained just by stimulus tuning. These analyses are compatible with a model of object recognition in cortex (Riesenhuber 2000) in which a population of shape-tuned neurons provides a general basis for neurons tuned to different recognition tasks.

COMP6043 Surveys

Overview of Surveys and Survey Systems. Class exercise sheet, to use to think about survey design example question types from survey monkey, plus set of example survey questions

Hiperautofluorescencia foveal como factor predictor de recuperación visual en pacientes con desprendimiento regmatógeno de retina

Introducción: una de las causas de pobre ganancia visual luego de un tratamiento exitoso de desprendimiento de retina, sin complicaciones, es el daño de los fotoreceptores, reflejada en una disrupción de la capa de la zona elipsoide y membrana limitante externa (MLE). En otras patologías se ha demostrado que la hiperautofluorescencia foveal se correlaciona con la integridad de la zona elipsoide y MLE y una mejor recuperación visual. Objetivos: evaluar la asociación entre la hiperautofluorescencia foveal, la integridad de la capa de la zona elipsoide y recuperación visual luego de desprendimiento de retina regmatógeno (DRR) exitosamente tratado. Evaluar la concordancia inter-evaluador de estos exámenes. Metodología: estudio de corte transversal de autofluorescencia foveal y tomografía óptica coherente macular de dominio espectral en 65 pacientes con DRR evaluados por 3 evaluadores independientes. La concordancia inter-evaluador se estudio mediante Kappa de Cohen y la asociación entre las diferentes variables mediante la prueba chi cuadrado y pruebas Z para comparación de proporciones. Resultados: La concordancia de la autofluorescencia fue razonable y la de la tomografía óptica coherente macular buena a muy buena. Sujetos que presentaron hiperautofluorescencia foveal asociada a integridad de la capa de la zona elipsoide tuvieron 20% más de posibilidad de recuperar agudeza visual final mejor a 20/50 que los que no cumplieron éstas características. Conclusión: Existe una asociación clínicamente importante entre la hiperautofluorescencia foveal, la integridad de la capa de zona elipsoide y la mejor agudeza visual final, sin embargo ésta no fue estadísticamente significativa (p=0.39)

Factores asociados a recuperación visual deficiente después de cirugía exitosa para desprendimiento de retina regmatógeno

Introducción: Varias características pueden afectar el pronóstico visual después de resolver quirúrgicamente el desprendimiento de retina. Existen características no observables por el ojo humano por si solo pero si por tomografía óptica coherente que se relacionan con la recuperación visual. Objetivo: Describir las características clínicas y topográfica en los periodos pre y postquirúrgico de ojos que ha sufrido DR regmatógeno con compromiso macular y su relación con la calidad de recuperación visual después de una cirugía considerada exitosa desde el punto de vista anatómico. Materiales y métodos: Estudio descriptivo en el que se comparan algunas características en tres periodos perioeperatorios, uno antes y dos después de cirugía (3 y 6 meses) de 24 ojos con DRregmatógeno y compromiso macular intervenidos mediante retinopexia combinada con vitrectomía pars plana. Resultados: La recuperación visual mejor o igual que logMAR 0,397 (20/50) se dió en 41,7% de ojos y 16,7%. alcanzaron agudeza visual logMAR 0,301 (20/40). Cinco ojos no alcanzaron una ganancia de líneas de visión mayor a cinco. El líquido submacular ausente se observó en la mayoría de ojos que recuperaron más de cinco líneas al igual que aquellos con elipsoide conservado. La regularidad del neuroepitelio y el edema en el periodo posquirúrgico no mostraron comportamientos claros respecto a recuperación visual al igual que la altura del desprendimiento y el número de cuadrantes afectados. Una mejor recuperación visual fue más frecuente en aquellos con menos de cinco semanas de desprendimiento de retina. Conclusiones: El retraso menor a cinco semanas en la resolución del desprendimiento de retina, la conservación del elipsoide y la ausencia de líquido submacular en el periodo postquirúrgico se observó más frecuentemente en ojos con mejor recuperación visual.