Os principais objetos de estudo dessa dissertação são uma estatística e um mapa da Província de São Paulo, ambos encomendados pela recém-instituída Assembleia Legislativa Provincial, em 1835, ao engenheiro-militar Daniel Pedro Müller (1785-1841). Planejados para serem utilizados como instrumentos de poder a serviço de grupos da elite paulista, no controle da administração provincial, a reconstituição dos contextos de sua produção, impressão e circulação permitem estabelecer nexos entre esses artefatos e a sociedade que os produziu e utilizou pela primeira vez, ampliando a compreensão da dinâmica política, econômica e social da Província paulista da primeira metade do Oitocentos. Para estudá-los buscou-se, inicialmente, reconstituir a trajetória de Daniel Pedro Müller, bem como caracterizar os grupos da elite paulista que passaram a ocupar os espaços de poder provincial a partir da transição do regime absolutista para a monarquia constitucional, no princípio da década de 1820, até o final da primeira metade daquele século. Em seguida, passou-se à análise dos artefatos propriamente ditos, buscando estabelecer relações entre esses objetos e os contextos político, econômico e social em que estavam inseridos. Por fim, a partir de dois exemplos concretos da economia política provincial a apropriação das terras indígenas para o avanço das culturas de exportação e subsistência em direção ao Oeste e a orientação da política econômica ao desenvolvimento da infraestrutura viária paulista buscou-se demonstrar como a construção territorial engendrada por estes artefatos serviu como instrumento de poder para a realização dos interesses e desígnios de autoridades administrativas em aliança com a elite mercantil-exportadora paulista. / The main study objects of this masters thesis are a statistic and a map of the Province of São Paulo, both commissioned in 1835 by the recently established Provincial Legislative Assembly to the military engineer Daniel Pedro Müller (1785-1841). Planned to be used as instruments of power to serve groups of the local elite in control of the provincial administration, the reconstitution of the contexts of its production, printing and circulation allows us to establish links between these artifacts and the society who produced and used them for the first time, expanding the comprehension of the political, economic and social dynamics of the Paulista province during the first half of the 19th century. In order to study these artifacts we sought, in the first place, to rebuild the trajectory of Daniel Pedro Müller as well as to characterize the Paulista elite groups that came to occupy the spaces of provincial power from the transition from the absolutist regime to the constitutional monarchy in the beginning of the 1820s, up to the end of the first half of that century. Afterwards we went to the analysis of the actual artifacts, aiming to establish relationships between these objects and the political, economic and social context in which they were entered. Finally, from two concrete examples of the provincial economic politics the appropriation of indigenous lands for the advancements of the exports and subsistence cultures towards the West part of the province and the guidance of the political economy for the development of the Paulista road infrastructure we aimed to demonstrate how the territorial construction engendered by these artifacts was used as an instrument of power to attend the interests and intends of administrative authorities in alliance with the São Paulo exporting-mercantile elite.

O objetivo principal de nosso trabalho é descrever e analisar criticamente o núcleo da teoria da gastrea de Ernst Haeckel. Ele gira em torno de duas noções principais: forma gastrular e metazoário. A teoria da gastrea é um conjunto de formulações que visa estabelecer uma definição de metazoário a partir da noção de forma gastrular. O argumento central da teoria da gastrea articula essas duas noções para organizar a partir de estudos de embriologia comparativa uma visão geral da história evolutiva do reino animal. / The main goal of our work is to describe and critically analyze the core of the gastrea theory of Ernst Haeckel. It centers around two main notions: gastrula form and metazoan. The gastrea theory is a set of formulations designed to establish a definition of metazoan from the notion of gastrula form. The central argument of the gastrea theory articulates these two notions to organize from studies of comparative embryology an overview of evolutionary history of the animal kingdom.

La dégénérescence maculaire liée à l’âge ou DMLA est une pathologie oculaire qui touche près d’un million de personnes en France, et représente la première cause de cécité légale dans les pays industrialisés. C’est une affection multifactorielle (environnement, génétique), dans laquelle les stress inflammatoires, métaboliques et oxydants interviennent et aboutissent à la mort des photorécepteurs. L’apparition des drusen (dépôts de matériel extracellulaire contenant de l’amyloïde-β (Aβ)), entre les cellules de l’épithélium pigmentaire de la rétine (EPR) et la membrane de Brush, représente un facteur de risque de développement de la DMLA. De plus, le 4-hydroxynonenal (4-HNE) est un marqueur de stress oxydant dans la rétine de patients de différentes pathologies dégénératives comme la DLMA. L’identification des mécanismes moléculaires et cellulaires impliqués dans les dégénérescences rétiniennes la pathogenèse de la DMLA constitue un enjeu de santé publique, puisqu’elle permettrait de développer de nouvelles stratégies thérapeutiques anti-dégénératives.Le but de mon travail de thèse a été dans un premier temps de mieux comprendre le rôle de l’Aβ dans la dégénérescence rétinienne.Nous avons montré que l’Aβ induit une activation rapide des cellules microgliales, une gliose soutenue des cellules gliales de Müller (CGM), un œdème dans la rétine interne et une apoptose des photorécepteurs. La dégénérescence des photorécepteurs est en corrélation avec une activation soutenue de PERK, impliquée dans la voie pro-apoptotique de la réponse UPR. Par ailleurs la gliose des CGM est caractérisé par une délocalisation des canaux Kir4.1, une diminution de l’expression d’AQP4 et de la glutamine synthetase (GS), et une augmentation de l’expression des canaux Kir2.1 et du transporteur GLAST1, suggérant une dérégulation de l’homéostasie rétinienne contrôlée par ces protéines. Nous avons montré que l’inhibition de la réponse inflammatoire, par l’utilisation de l’indomethacine, un inhibiteur non stéroïdien de de la cyclooxygénase (COX) 2, réverse l’effet de l’Aβ sur l’expression des canaux Kir4.1 et sur GLAST1 mais pas celle de la GS et d’AQP4, suggérant un couplage partiel entre la gliose et la réponse inflammatoire dans notre modèle d’injection sous-rétinienne d’Aβ.Dans un deuxième temps, nous nous sommes intéressés au rôle du 4-HNE dans les CGM, un produit de peroxydation lipidique, qui est produit dans la rétine sous l’effet de l’Aβ. Nous avons observé qu’un stress oxydant unique et létal induit par le 4-HNE, entraîne la mort des CGM par apoptose dépendante de l’activation des caspases. L’utilisation d’antioxydants impliqués dans la régénération du glutathion (GSH), protège contre la mort des CGM. L’analyse du transcriptome des CGM soumises au 4-HNE a permis de mettre en évidence une réponse transcriptionnelle adaptative des CGM : une activation de la défense anti-oxydante, de la réponse UPR (unfolded protein response) au stress du réticulum endoplasmique, et un phénotype anti-inflammatoire. Par ailleurs, la surexpression de l’APP (amyloid protein precursor), dont l’expression du transcrit est augmentée sous l’effet du stress oxydant dans les CGM, protège ces cellules contre la mort induite par le 4-HNE. Cette protection est associée à une augmentation des capacités anti-oxydantes et à une activation de la voie de survie de la réponse UPR. L’ensemble de nos résultats montre un rôle de l’Aβ dans la dégénérescence des photorécepteurs et indique que le métabolisme de l’APP, ainsi que les voies de survie et pro-apoptotique de la réponse UPR pourraient constituer des cibles thérapeutiques contre la dégénérescence rétinienne induite par l’Aβ ou les stress oxydants. / Age related macular degeneration (AMD) is a leading cause of blindness in western countries and affects one million people in France. Multiple risk factors (genetics, environment) are involved in the pathogenesis of AMD. In addition, the AMD pathogenesis is strongly associated with chronic oxidative stress and inflammation that ultimately lead to photoreceptor death. AMD is characterized by the formation of drusen, extracellular deposits, including amyloid-β (Aβ), between the retinal pigmented epithelium and Bruch’s membrane. Moreover, 4-hydroxynonenal (4-HNE) is an oxidative stress marker of different retinal diseases including AMD. The determination of molecular and cell mechanisms involved in retinal degeneration and the pathogenesis of AMD is required in order to develop new therapeutic anti-degenerative approaches. The aim of our study was first to investigate the role of Aβ in retinal degeneration. We demonstrated that subretinal injection of Aβ induces an early activation of microglial cells, a sustained retinal Müller glial (RMG) cells gliosis, an oedema in the internal part of retina and photoreceptors apoptosis. The photoreceptors apoptosis was correlated with a sustained activation of PERK, a kinase implicated in the pro-apoptotic pathway of UPR (unfolded protein response). In addition, RMG gliosis has been characterized by a Kir4.1 channel redistribution, a down-regulation of AQP4 and glutamine synthetase (GS) expression, and an up-regulation of Kir2.1 channel and GLAST1 transporter expression, suggesting a dysregulation of the retinal homeostasis which is controlled by these proteins. The inhibition of the inflammatory response using indomethacin, a non-steroidal and non-specific cyclooxygenase (COX) 2 inhibitor, reversed Aβ-induced Kir4.1 channel redistribution and GLAST1 up-regulation but not GS and AQP4 down-regulation, suggesting a partial coupling between gliosis and inflammatory response in retinal degeneration after subretinal injection of Aβ in mice. The second part of our study aimed to investigate the effects on RMG cells of 4-HNE, a lipid peroxidation product that is up-regulated in retina after Aβ injection. We have shown that a single lethal oxidative stress using 4-HNE induces RMG cells apoptosis associated with caspase 3 and caspase 9 activation. Pre-treatment of RMG cells with anti-oxidative molecules involved in glutathione regeneration restored cell viability. Transcriptome analysis of RMG cells treated with 4-HNE showed an adaptive transcriptional response consisting in an activation of anti-oxidative stress cell defense, activation of UPR in response to endoplasmic reticulum stress and anti-inflammatory phenotype. APP (amyloid protein precursor) overexpression, which the transcript is up-regulated in RMG cells under oxidative stress, protects from 4-HNE-induced cell death. This protection is associated with an up-regulation of anti-oxidative cell defense and an activation of the pro-survival pathway of UPR. Our study pinpoints the role of Aβ in photoreceptors degeneration and suggests that targeting APP metabolism, pro and anti-apoptotic pathways of the UPR response may hel develop selective methods against retinal degeneration implicating Aβ and oxidative stress.

La rétinopathie de la prématurité (ROP) est un trouble oculaire potentiellement aveuglant chez les nourrissons prématurés, qui est causé par la formation d'une néovascularisation rétinienne aberrante (NV). Des études récentes ont démontré que les cellules de Müller sont les principaux producteurs de cytokines inductrices d'inflammation et de facteurs de croissance dans des conditions pathologiques. Par ailleurs, le recrutement des macrophages est significativement augmenté au cours de la NV rétinienne, ce qui a un rôle proangiogénique dans la ROP. Par conséquent, nous avons émis l'hypothèse que les LMP inhibent la NV pathologique de la rétine en ciblant les cellules de Müller dans le modèle murin de rétinopathie induite par l'ischémie (OIR). Nous avons démontré que les microparticules lymphocytaires (LMP) dérivées de lymphocytes T CEM humains pendant l'apoptose possèdent une grande capacité angiostatique. Dans notre étude actuelle, nous avons étudié l'effet des LMP in vitro et in vivo. In vitro, l'influence des LMP sur les propriétés des cellules de Müller a été déterminée en utilisant des cellules de Müller de rat rMC-1 et des macrophages murins RAW 264.7. Les résultats ont révélé que les LMP étaient internalisées par rMC-1 et réduisaient la prolifération cellulaire de rMC-1 en fonction de la dose, sans induire l'apoptose cellulaire. Les LMP ont inhibé la capacité chimiotactique de rMC-1 sur RAW 264.7, ainsi que l'expression des chimiokines (VEGF et SDF-1) dans rMC-1. In vivo, l'injection intra-vitréenne de LMP a été internalisée par les cellules de Müller. Les LMP ont atténué la NV aberrante de la rétine et l'infiltration des macrophages en partie par l'expression réduite des chimiokines (VEGF et SDF-1). De plus, les LMP régulent la baisse d'expression de ERK1 / 2 et HIF-1α dans les cellules Müller. Nos résultats actuels élargissent notre compréhension des effets des LMP, fournissant des évidences que les LMPs sont un traitement potentiel pour les maladies rétiniennes en lien avec la NV. / Retinopathy of prematurity (ROP) is a potentially blinding ocular disorder in premature infants. It is caused by the formation of aberrant retinal neovascularization (NV). Recent studies have demonstrated that Müller cells are the primary producers of inflammation-inducing cytokines and growth factors in pathological conditions. Additionally, the recruitment of macrophages is significantly increased during retinal NV, which exerts a proangiogenic role in ROP. Lymphocytic microparticles (LMPs) are small membrane-wrapped vesicles released from human CEM T lymphocytes, which is a cell line of acute lymphoblastic leukemia. In our previous studies, we demonstrated that LMPs derived from apoptosis-induced human CEM T lymphocytes possess potent angiostatic capacities. Therefore, we hypothesized that LMPs inhibit pathological retinal NV via targeting Müller cells in an ischemia-induced retinopathy mouse model. In this study, we investigated the effect of LMPs both in vitro and in vivo. In vitro, we determined the influence of LMPs on Müller cell properties using rat Müller cells rMC-1 and murine macrophages RAW 264.7. The results revealed that LMPs were internalized and reduced cell proliferation of rMC-1 dose-dependently without inducing cell apoptosis. LMPs also inhibited the chemotactic capacity of rMC-1 on RAW 264.7, as well as the expression of the chemokines (VEGF and SDF-1) in rMC-1. In vivo, we intravitreally injected LMPs and found that LMPs was internalized by Müller cells. LMPs attenuated aberrant retinal NV and the infiltration of macrophages. LMPs also downregulated the expression of angiogenic factors/chemokines (VEGF and SDF-1) in Müller cells. Furthermore, LMPs downregulated the expression of ERK1/2 and HIF-1α in Müller cells. These findings expand our understanding of the effects of LMPs, providing evidence that LMPs are a potential treatment for retinal NV diseases.

Les maladies dégénératives de la rétine sont une des causes principales de cécité. Parmi différentes stratégies thérapeutiques actuellement étudiées, notre équipe s’intéresse au potentiel régénératif de la rétine. Une source cellulaire d'intérêt sont les cellules de Müller, principal type de cellules gliales de la rétine, capables de se réactiver en cas de dégénérescence et d’adopter certaines caractéristiques de cellules souches. Elles entrent alors dans un état appelé gliose réactive. Tandis que chez certaines espèces comme le poisson, elles permettent la régénération de la rétine, elles ont des capacités régénératives très limitées et inefficaces chez les mammifères. Une meilleure connaissance des mécanismes moléculaires régissant la gliose réactive des cellules de Müller est donc essentielle si l’on veut identifier des cibles thérapeutiques capables de stimuler le potentiel de régénération de ces cellules. Dans ce contexte, le but de mon projet de thèse a été d’étudier le rôle du co-facteur de transcription YAP dans la réactivation des cellules de Müller. Cette protéine est l’effecteur de la voie de signalisation Hippo, connue pour son implication dans la régulation des cellules souches et la régénération de certains organes.Dans un premier temps, nous avons réalisé une analyse transcriptomique qui a montré que la voie Hippo/YAP est une des principales voies dérégulées dans un modèle de dégénérescence rétinienne chez la souris. Nous avons ensuite montré que la protéine YAP est spécifiquement exprimée dans les cellules de Müller et que son expression et son activité transcriptionnelle sont augmentées au cours de la dégénérescence lorsque les cellules de Müller deviennent réactives. Ces données suggèrent pour la première fois un lien entre YAP et la gliose réactive dans la rétine. Par conséquent, dans un second temps, mon projet de thèse a consisté en l’étude fonctionnelle de YAP dans les cellules de Müller. Dans ce but, nous avons généré par croisements chez la souris un modèle inductible de délétion du gène Yap spécifiquement dans ces cellules. Ce modèle a permis de montrer qu’en absence de Yap en conditions physiologiques, plusieurs gènes spécifiques des cellules de Müller sont dérégulés, suggérant un dysfonctionnement de ces cellules. L’étude phénotypique a permis de révéler que ces dérégulations moléculaires conduisent à un vieillissement prématuré des cellules de Müller et à une baisse de la vision chez les souris âgées. Ces données suggèrent que YAP est requis pour le fonctionnement normal des cellules gliales de Müller. Nous avons ensuite examiné l’impact de la perte de Yap dans les cellules de Müller en conditions de dégénérescence des photorécepteurs. Une analyse transcriptomique a permis de montrer que différents aspects de la réponse moléculaire des cellules de Müller réactives sont affectés. Parmi les processus biologiques dérégulés, nous nous sommes intéressés à la régulation de la prolifération cellulaire. Nous avons montré que YAP est nécessaire à l’augmentation de l’expression de gènes associés à la réentrée dans le cycle cellulaire de la glie de Müller. Par ailleurs, nos résultats suggèrent que des composants de la voie de signalisation EGFR, connue pour son rôle central dans la réactivation des cellules de Müller, sont régulés par YAP.Dans l’ensemble, ces résultats révèlent l’importance de YAP (i) dans le fonctionnement des cellules de Müller en conditions physiologiques pour maintenir l’homéostasie rétinienne, et (ii) dans la régulation des processus de réactivation de ces cellules en conditions dégénératives. De plus, ces données permettent de proposer un modèle selon lequel YAP serait impliqué dans le contrôle de la réentrée des cellules de Müller dans le cycle cellulaire via une interaction avec la voie de signalisation EGFR. Ce travail a donc contribué à approfondir nos connaissances du réseau de signalisation impliqué dans la réactivation des cellules de Müller de la rétine des mammifères. / Retinal dystrophies are one of the main causes of blindness. Among the different therapeutic strategies currently studied, our team is interested in the regenerative potential of endogenous retinal cells. A cellular source of interest are Müller cells, which are the main type of glial cells in the retina. These cells are able to reactivate in case of retinal degeneration and adopt various characteristics of stem cells. They enter a state called reactive gliosis. While in some species such as the fish, they allow the complete regeneration of the retina, they have very limited and ineffective regenerative capacities in mammals. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of promising new therapeutic strategies. In this context, the aim of my thesis project was to study the role of the co-transcription factor YAP in Müller cells reactivation. This protein is the main effector of the Hippo signaling pathway which is a crucial player in the field of stem cell biology and regeneration.As a first step, we performed a transcriptomic analysis, which revealed that the Hippo/YAP pathway is one of the main signaling deregulated in a mouse model of photoreceptor degeneration. In particular, we found that YAP is specifically expressed in Müller cells and strongly upregulated upon retinal degeneration, when these cells are reactivated. We thus uncovered for the first time a link between the Hippo/YAP pathway and reactive gliosis in the retina. Consequently, the second part of my thesis project was to undertake a functional study of YAP in Müller cells. For this purpose, we generated, by crossing, a mouse model allowing for Yap conditional knockout specifically in these cells. This model allowed us to show that Yap deletion leads to deregulation of several Müller cell specific genes. A phenotypic analysis revealed that these molecular deregulations lead to premature aging of Müller cells and visual defects in old mice. These results suggest that YAP is required for normal function of Müller glial cells. We then studied the impact of Yap deletion in Müller cells under degenerative conditions. A transcriptomic analysis revealed that various aspects of the molecular response of reactive Müller cells are affected in the absence of Yap. Among the deregulated biological processes, we focussed in particular in the regulation of cell proliferation. We found that YAP is required to trigger cell cycle gene upregulation that occurs in Müller glial cells following photoreceptor cell death. Furthermore, our results suggest that some components of the EGFR signaling pathway, which is known for its central role in the reactivation of Müller cells in pathological conditions, are regulated by YAP in Müller cells.Taken together, these results highlight the importance of YAP (i) in Müller cell function under physiological conditions to maintain retinal homeostasis, and (ii) in the regulation of Müller cell reactivation process under degenerative conditions. Moreover, these data allow us to propose a model in which YAP would be involved in the control of Müller glia cell cycle re-entry through its interaction with the EGFR signaling pathway. Therefore, this work has contributed to increase our knowledge of the signaling network involved in the reactivation of Müller cells in the mammalian retina.

(in English): The presented PhD thesis deals with two artists, Emanuel Hegenbarth (1868-1923) and Richard Müller (1874-1954). Both were Czech Germans, i.e. of German nationality, using German as their vernacular language, born in the second half of the 19th century in Bohemia the territory of the former Austro-Hungarian Empire (nowday's Czech Republic) and later have been working for a long time in Dresden. This initial reality represented a different starting point for each of them and played a different role in their later life and artistic trajectory. Richard Müller did not lose contact with his bohemian homeland during his lifetime, but he did not have strong ties to it and considered Dresden his home and background. He was particularly influential as a professor at the Dresden Academy, a position he held for more than thirty years. His artistic principles and creative activity shaped the emerging generation of artists, which included representatives of German-speaking artists from Bohemia, Moravia and Silesia who passed through his studio. The thesis includes an excursus devoted to Herbert Seemann (1900-1945), in whose work Müller's influence is most evident. A different approach can be found in Emanuel Hegenbarth, who, despite his professorship at the Dresden Academy, maintained intensive and...

A civil Uprising on 17 June 1953 in the German Democratic Republic created a dilemma for a number of writers there. On one hand, they were deeply committed to the principles of socialism, upon which their state was based and which they saw as being put in grave danger by events such as those they experienced on 17 June. On the other hand, they were fiercely critical of the practice of socialism as pursued by the governing party, whose Stalinist methods of governance they believed to be in large part responsible for the civil unrest. My thesis explores the nature of this dilemma in the case of four writers, Bertolt Brecht, Heiner Müller, Stefan Heym and Erich Loest, and their efforts to resolve it within a repressive state, whose regime vigorously suppressed all signs of criticism or dissent. These writers created major works of fiction, a cycle of poems, a drama and two novels, in which the Uprising of 17 June is the central theme. In addition, each has provided a substantial body of non-fictional texts, largely journalistic and autobiographical, in which the Uprising is extensively contextualised. In bringing together and interrelating the fictional and non-fictional work of each author into my analysis, I have been able to demonstrate that all four held and publicly expressed views that set them in opposition to the regime in the GDR.

A chamada hermenêutica tradicional tem se mostrado impotente desde a Constituição de Weimar em acompanhar e explicar a transformação por que passaram as Constituições no século XX. Por outro lado, a moderna metodologia de interpretação da Constituição ampliou demasiadamente a importância do fator político, empobrecendo a consistência jurídica da Constituição, conduzindo a sua concretização a um estado de crise. Porém, não é possível desprezar as novas metodologias, especialmente naqueles países onde a democracia está longe de resolver as questões sociais. A Metódica Estruturante de Friedrich Müller, inserindo-se no rol das novas metodologias, intenta superar a deficiência verificada nas modernas teorias, assim como nas teorias tradicionais. Desenvolveu-se ela com base na experiência constitucional alemã e tratou de inúmeros temas da teoria jurídica, aproveitando o presente trabalho apenas o núcleo metodológico principal dessa teoria, a sua metódica jurídica, que consiste precisamente em uma particular concepção de estrutura da norma, que se revela num processo de concreção normativa. Pretende-se realizar o estudo dessa metódica, aplicando-a às decisões proferidas pelo Supremo Tribunal Federal no âmbito da ordem econômica, de modo a verificar conclusivamente a conformidade ou não dessa teoria com o modo como os magistrados da Corte Suprema estruturam seus votos. Assim, o objeto de trabalho da análise é a argumentação jurídica e a pergunta que se fará é, por um lado, em que medida a metódica estruturante descreve a organização argumentativa das decisões do STF e, de outro lado, em que medida apresenta-se estruturada a argumentação jurídica das decisões do STF à luz da metódica. Ao final, conclui-se que as decisões proferidas pelo Supremo não adotam um padrão de organização que siga um modelo estruturado como aquele erigido pela Metódica Estruturante / Since the Weimar Constitution, the so called Traditional Hermeneutics has been incapable of dealing with the changes occurred in the XX century constitutions. On the other hand, the modern theories have excessively enlarged the boundaries of interpretation, leading to a critical situation in this sector. Friedrich Müller theory, in spite of being a modern theory, intends to overcome these mentioned deficiencies. It was developed within the German constitutional experience and only the main core of it, the law methodic, will be important for the purposes of this work. Therefore, the objective of this work is to apply Müllers law methodic to the decisions taken by the Brazilian Supreme Court in the field of constitutional economic order. At the end, the work concluded that the Brazilian Supreme Court decisions, in the field of the constitutional economic order, do not comply with a structural model of decisions like the one developed by Friedrich Müller.

Retinal ganglion cells play a crucial role in the relay of visual signals from the eye to the brain. This cell type is affected and eventually lost in the eye disease glaucoma, resulting in progressive and irreversible loss of vision. Studies of the molecular mechanisms leading to retinal ganglion cell death are important for the understanding of the disease and for designing future treatments. This thesis addresses and studies these molecular mechanisms, including alterations in gene expression after experimental retinal injuries. The effects of a neuroprotective drug, brimonidine, after transient retinal ischemia were also studied in order to help explain the mechanisms behind the protective properties of this drug. Several methods, including quantitative reverse transcriptase PCR, micro-arrays, western blot and immunohistochemistry, were used. The results showed that transient retinal ischemia triggers cell division in Müller cells and alters the gene expression of growth factors, their receptors, and intermediate filaments in the retina. Several genes related to the apoptosis process were less affected. Pre-treatment with brimonidine increased the levels of certain growth factors (BDNF, NT3, CNTF, FGF9) compared with vehicle. Brimonidine also had marked effects on genes related to progenitor cells, among them the recognized neural stem cell marker nestin. The increase in levels of nestin after ischemia was countered by brimonidine treatment. Moreover, retinal ganglion cell death following either optic nerve transection or optic nerve crush appears to involve the extrinsic apoptotic pathway although the gene expression response appears to differ between these injuries. The results obtained in this work contribute to an increased understanding of retinal injuries and highlight the importance of Müller cells in the endogenous defense against retinal injuries.

Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2018-07-17T18:47:50Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Loren_Cristine_Ferreira_Cuadros.pdf: 4331024 bytes, checksum: 6f0813758e58cdd14dc44163a7ad1238 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-07-17T21:24:48Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Loren_Cristine_Ferreira_Cuadros.pdf: 4331024 bytes, checksum: 6f0813758e58cdd14dc44163a7ad1238 (MD5) / Made available in DSpace on 2018-07-17T21:24:57Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Loren_Cristine_Ferreira_Cuadros.pdf: 4331024 bytes, checksum: 6f0813758e58cdd14dc44163a7ad1238 (MD5) Previous issue date: 2017-12-21 / Sem bolsa / O artista plástico alemão Gerhard Richter tem causado certa controvérsia com sua abordagem do Holocausto que utiliza a técnica da pintura abstrata. Uma de suas obras mais recentes, “Birkenau”, tem como pano de fundo as fotografias tiradas pelos prisioneiros judeus que integravam o Sonderkommando em 1944. Alguns críticos acusam o trabalho de Richter de esconder a verdade de Auschwitz. Por sua vez, o romance “Tudo o que tenho levo comigo”, da escritora romeno-alemã Herta Müller, é constituído por uma série de imagens poéticas que são produto da visão pictórica de seu narrador, Leo Auberg. Aos dezessete anos, o jovem romeno é deportado para um gulag após a ocupação de seu país pelas tropas soviéticas e encontra na observação da beleza dos elementos de seu cotidiano no campo de trabalhos forçados uma forma de resistir à violência física e psicológica a que é submetido. O presente trabalho tem como objetivo sugerir que em vez de encobrir os horrores dos campos de concentração e de trabalhos forçados, a estetização presente nas obras de Richter e Müller evidencia a crueldade dos crimes cometidos pelos nazistas e soviéticos. / The German artist Gerhard Richter has caused some controversy through his use of the abstract painting technique to approach the Holocaust. One of his most recent works, “Birkenau”, uses as its background images the photographs taken by some of the Jewish prisoners who were part of the Sonderkommando group in 1944. Some critics accuse Richter of hiding Auschwitz’s truth. On its turn, “The Hunger Angel”, a novel by Romanian-born German author Herta Müller, consists of successive poetic imagery arising from the picturesque vision of its narrator, Leo Auberg. At the age of seventeen, the young Romanian is deported to a gulag after the occupation of his country by Soviet troops and finds in observing the beauty of the elements of his daily life at the forced labor camp a way of resisting the physical and psychological violence to which he is subjected. This research project aims to suggest that instead of concealing the horrors of the concentration and forced labor camps, the aestheticization found in Richter's and Müller's works emphasizes the cruelty of the crimes committed by the Nazis and Soviets.