A toxoplasmose ocular é atribuída ao parasita, mas a auto-imunidade pode participar do processo. Soros humanos com IgG positiva para T. gondii mostraram níveis altos de IgG anti-retina para diferentes antígenos, se comparados com soros negativos para T. gondii, uveítes de outras origens também tiveram títulos elevados. Hamsters imunizados e/ou infectados não mostraram estes anticorpos sem mimetismo antigênico. A retinocoroidite por Toxoplasma induz resposta humoral auto-imune contra antígenos da retina, provavelmente piorando o efeito direto do agente. Estes anticorpos podem ser usados como marcadores de doença ocular em pacientes soropositivos para toxoplasmose pela triagem de lesão ocular. / Ocular toxoplasmosis is attributed to the parasite, but autoimmunity could have a role in this process. Human sera, positive of anti-T. gondii IgG, show high levels of anti-retina IgG, measured by several antigens, as compared to T. gondii seronegative samples. Sera from patients with uveitis from other origins also had higher anti-retina abs levels. Challenged and/or immunized hamsters showed low anti-retina abs levels, without antigen mimicry. Toxoplasmic retinochoroiditis presents a humoral anti-retina abs, probably worsening the parasite direct effect. Those antibodies could be used as markers of eye involvement in toxoplasmosis seropositive patients, as a screening for eye examination.

The eye contains closely related but widely different tissues, offering a unique opportunity to investigate the phenotype and function of monocyte-derived cell populations within functionally unique microenvironments in a single complex organ. The uveal tract and retina contain rich networks of immune cells that reside and traffic through the eye, these cells having been implicated in various ocular inflammatory processes and immune-mediated diseases. One such inflammatory condition is human posterior uveitis, an autoimmune disease mainly affecting the retina. As current treatments for posterior uveitis only serve to slow down disease progression, studies using animal models, namely, experimental autoimmune uveoretinitis (EAU), have focused on determining the key cellular and molecular mediators involved in disease initiation in order to expand the potential for novel therapeutic applications. The overall purpose of experiments in this thesis was to explore monocyte-derived cell populations of the uveal tract and retina, this being achieved by utilising a novel transgenic mouse model. Cx3cr1gfp/gfp transgenic mice on both BALB/c and C57Bl/6 backgrounds contain an enhanced green fluorescent protein (eGFP) encoding cassette knocked into the Cx3cr1 gene, disrupting its expression but facilitating GFP expression under the control of the Cx3cr1 promoter. Heterozygous (Cx3cr1+/gfp) mice were generated by crossing Cx3cr1gfp/gfp mice to wild-type (WT) mice. This transgenic model allowed for the exquisite visualisation of Cx3cr1-bearing monocyte-derived dendritic cells (DC) and macrophages in ocular tissues, whilst also enabling the investigation of a potential role for Cx3cr1 in recruiting monocyte-derived cells to the eye in steady-state and inflammatory conditions.

Influence of stress factors on tunneling nanotubes in cultivated human retinal pigment epithelial cells (ARPE-19). The eye as one of the most important sense organs of the human body is exposed to visible light radiation and other stress factors every day. Especially the retina (of the eye) is a sensible tissue for oxidative damage (Wu et al., 2006). The retinal pigment epithelium (RPE) is an important layer of the retina, which forms the outer layer and phagocytises the shed disc membranes of the photoreceptor outer segments. Furthermore, the RPE is involved in the maintenance of the visual cycle and regulates the retinal balance (Bok, 1993). To maintain those functions, a steady communication between the RPE-cells and the adjacent neighbour cells is necessary. Tunneling nanotubes (TNTs) build a newly discovered variety of cell communication and thus establish intercellular signal transduction and transport different cell components including pathogens (Rustom et al., 2004; Onfelt et al., 2006; Sherer und Mothes, 2008; Veranic et al., 2008). The formation of TNTs in the neuron-like pheochromocytoma cell line PC12 was first reported by Rustom et al in 2004. In the following years a growing number of cell types containing TNTs were described. For example a lot of TNT-reports were found between immune cells (Onfelt et al., 2004; Sowinski et al., 2008). Chinnery et al. first described TNTs in vivo in 2008. Here they found TNTs between dendritic cells in the cornea of the mouse. An important characteristic of TNTs is that they do not attach to the substratum. They contain F-actin as a characteristic feature of there structure (Rustom et al., 2004). Our study group detected the formation of TNTs between ARPE-19-cells, a human retinal pigment epithelial cell line. They contain F-actin, but no microtubules. Further it was observed an exchange of electrical signals, small molecules and even the transfer of organelles between cells via TNTs (see publication Wittig et al., 2012). It is often described in the literature, that TNTs are very sensitive against stress factors, like prolonged light excitation, mechanical and chemical stress, which then can result in rupture of the TNTs (Rustom et al., 2004; Koyanagi et al., 2005; Gurke et al., 2008a; Pontes et al., 2008; Sowinski et al., 2008; Domhan et al., 2011; Wang und Gerdes, 2012). Up to now it is widely unclear how pathological conditions influences TNTs. There are several studies, which report an induction but also an inhibition of TNT-formation by different factors. The reaction of cell-cell-interactions between RPE cells on stress factors is not jet analysed. So our motivation was, to analyse the influence of different stress factors on the number, the morphology and formation of TNTs. ARPE-19-cells were treated with blue light, with a wavelength of 470 and 405 nm, with 3000 μM glyoxal, with 200 μM H2O2, with medium without serum as well as with cytochalasin-D and latrunculin-B. With the help of differential interference contrast (DIC) microscopy the formed TNTs were counted and the morphology was evaluated. A 24 hours cultivation of untreated ARPE-19 cells resulted in 15 TNTs per 100 cells on average. After excitation of the ARPE-19-cells with blue light 470 and 405 nm the number of TNTs decreased 50 % and 28,5 % accordingly in comparison to untreated cells (100 %). Furthermore, the cell culture, which was treated with glyoxal and H2O2 resulted in a reduction of 17,5 % and 53 % TNTs in comparison to the untreated cell culture. Cells which were cultured with serum free medium had an decreased TNT-number of 56.8 % in comparison with serum containing medium. TNTs of untreated ARPE-19-cells have a diameter from 50 to 300 nm (Wittig et al., 2012). Every TNTs, which were formed under named stress factors had the same diameter like untreated cells. In this study an average TNT length of 23 +/- 16 μm was measured between cells without treatment. This correlated with the TNT-lengths of cells which excitated with blue light 405 and 470 nm with 26 +/- 13 μm and 24 +/- 14 μm. In contrast the TNT-lenghts of cells treated with glyoxal and H2O2 with 16 +/- 11 μm and 15 +/- 13 μm were less and from cells cultured without serum with 34 +/- 20 μm were above the average length of TNTs of untreated cells. TNTs of ARPE-19-cells without treatment and TNTs which were treated with stress factors contained F-actin but no microtubules. Depolymerisation of F-actin, induced by addition of cytochalasin-D or latrunculin-B, led to disappearance of TNTs. This is an evidence for the importance of F-actin as an essential component of TNTs between ARPE-19-cells. Under the influence of blue light excitation the TNTs formed as good as untreated cells after contact of migrating cells. Reason for the reduced TNT-formation under stress factors could be explained by the generation of oxidative stress due to reactive oxygen species (ROS). ROS induced under blue light- or glyoxal-treatment as well as H2O2 could influence cell function by inactivation of cell-mediated proteins or induction of F-actin oxidation with subsequent destruction of the actin-network and inhibition of the actin-polymerisation (Chen, 1993; Ballinger et al., 1999; Thornalley et al., 1999; Valen et al., 1999; Dalle-Donne et al., 2002; Nilsson et al., 2003; Shangari und O'Brien, 2004; Zhu et al., 2005; Knels et al. 2008; Roehlecke et al., 2009). The reduced actin-polymerisation as well as the disruption of the TNTs due to changes at the actin-cytoskeleton and at the membranes could explain the reduced TNT-formation (Valen et al., 1999; Dalle-Donne et al., 2002; Reber et al., 2002; Zhu et al., 2005; Knels et al., 2008). The inhibition of the cell growth under oxidative stress conditions and under nutritional deficiency by serum free medium could lead to a reduced TNT-formation too. In this study we found a reduction of TNT-number between ARPE-19-cells under different stress conditions. It is possible, that TNTs are formed between RPE- and photoreceptor-cells in vivo, where they can exchange useful or recyclable materials between cells (Wang et al., 2011; Wittig et al., 2012). Disruption of TNTs by reactive oxygen species could cause a decreased exchange of informations. It is possible, that the cells, RPE- as well as photoreceptor-cells, die due to a deficiency of nutrients. This could be another reason in the formation of age related macular degeneration, which shows a destruction of RPE-cells and secondary of the photoreceptorcells. / Das Auge ist als eines der wichtigsten Sinnesorgane des Menschen täglich sichtbarer Lichtstrahlung und weiteren Stressfaktoren ausgesetzt. Die Netzhaut des Auges ist besonders empfindlich für oxidative Schäden (Wu et al., 2006). Eine bedeutende Schicht der Netzhaut im Auge stellt das retinale Pigmentepithel (RPE) dar, welches die äußere Schicht der Retina bildet und täglich die abgeworfenen Photorezeptoraußensegmentscheiben phagozytiert. Zudem ist das RPE wesentlich am visuellen Prozess sowie der Aufrechterhaltung des retinalen Gleichgewichts beteiligt (Bok, 1993). Um diese Funktionen zu gewährleisten, ist eine ständige Kommunikation zwischen den RPEZellen sowie zu angrenzenden Nachbarzellen innerhalb der Netzhaut notwendig. So ist über Tunneling Nanotubes (TNTs), als neu entdeckte Kommunikationsform, ein interzellulärer Transport von Signalen und verschiedensten Zellkomponenten, aber auch von Pathogenen, möglich (Rustom et al., 2004; Onfelt et al., 2006; Sherer und Mothes, 2008; Veranic et al., 2008). Erstmals 2004 beschrieben Rustom et al. die Bildung von TNTs zwischen Rattennierenzellen in vitro. In den folgenden Jahren kam es zu einer Vielzahl weiterer TNT-Entdeckungen zwischen verschiedensten Zellen in vitro. So findet man zum Beispiel vermehrt TNTBeschreibungen zwischen Immunzellen (Onfelt et al., 2004; Sowinski et al., 2008). Ein erster Nachweis an TNTs in vivo erfolgte 2008 durch die Arbeitsgruppe Chinnery et al.. Hierbei fand man TNTs zwischen dendritischen Zellen in der Mauscornea. Ein wichtiges Merkmal von TNTs ist, dass sie sich als frei im Medium schwebende interzelluläre Verbindungen darstellen, ohne Kontakt zum Substrat zu haben. TNTs sind im Wesentlichen als stabilisierendes Hauptstrukturmerkmal aus Aktin aufgebaut (Rustom et al., 2004). In unserer Arbeitsgruppe wurde die Bildung von TNTs zwischen ARPE-19-Zellen, einer humanen Pigmentepithelzelllinie, entdeckt. Neben dem strukturellen Aufbau aus Aktin, konnte ein Austausch von elektrischen Signalen sowie molekularen Stoffen und der Transport von Organellen (Mitochondrien) durch TNTs zwischen ARPE-19-Zellen nachgewiesen werden (siehe Publikation Wittig et al., 2012). Wie schon mehrfach in der Literatur beschrieben, reagieren TNTs sehr sensibel auf Stressfaktoren, so zum Beispiel auf längere Lichtreizung, mechanischen und chemischen Stress, was jeweils zur Ruptur der Strukturen führen kann (Rustom et al., 2004; Koyanagi et al., 2005; Gurke et al., 2008; Pontes et al., 2008; Sowinski et al., 2008; Domhan et al., 2011; Wang und Gerdes, 2012). Weitgehend unklar ist bisher der Einfluss von pathologischen Bedingungen auf die TNTs. Es gibt mehrere Studien, in denen durch verschiedenste Faktoren über eine Induktion, aber auch über eine Hemmung der TNT-Bildung berichtet wurde. Die Reaktion von Zell-Zell-Interaktionen zwischen RPE-Zellen auf Stressfaktoren wurde bisher in wissenschaftlichen Arbeiten nicht untersucht. Dies nahmen wir zum Anlass, den Einfluss von unterschiedlichen Stressfaktoren auf die Anzahl von TNTs, ihre Morphologie und Bildung zu untersuchen. Es erfolgte eine Behandlung der ARPE-19-Zellen mit Blaulicht in den Wellenlängen 405 und 470 nm, mit 3000 μM Glyoxal, mit 200 μM H2O2, mit serumfreiem Medium sowie mit Cytochalasin D und Latrunculin B. Die gebildeten TNTs wurden anschließend mit Hilfe der Lichtmikroskopie ausgezählt sowie deren Morphologie beurteilt. So bildeten unbehandelte ARPE-19-Zellen nach 24 Stunden Kultivierung im Durchschnitt 15 TNTs pro 100 Zellen aus. Nach 24stündiger Bestrahlung der ARPE-19-Zellen mit Blaulicht 470 nm und 405 nm fiel die TNT-Anzahl auf 50 % und 28,5 % im Vergleich zu unbehandelten Zellen (100 %). Weiterhin fanden sich in den Glyoxal- und H2O2-behandelten Kulturschalen 17,5 % und 53 % TNTs verglichen mit der unbehandelten Zellkultur. In der serumfreien Kulturschale verringerten sich die TNTs 24 Stunden nach Ausplattierung der Zellen auf 56,8 % im Vergleich zu in Medium mit Serum kultivierten Zellen. TNTs unbehandelter ARPE-19-Zellen besitzen einen Durchmesser von 50 bis 300 nm (Wittig et al., 2012). Alle unter oben genannten Stressfaktoren gebildeten TNTs befanden sich in Hinblick auf ihren Durchmesser im Bereich der TNTs unbehandelter Zellen. Bei TNTs unbehandelter Zellen wurde in dieser Arbeit eine durchschnittliche Länge von 23 +/- 16 μm gemessen. Dies entsprach dem TNT-Längendurchschnitt von mit Blaulicht 405 nm und 470 nm bestrahlter ARPE-19-Zellen mit 26 +/- 13 μm und mit 24 +/- 14 μm. Unter Glyoxal und H2O2 gebildete TNTs lagen im Gegensatz dazu mit 16 +/- 11 μm und 15 +/- 13 μm unterhalb und unter serumfreier Kultivierung mit 34 +/- 20 μm über dem TNTLängendurchschnitt unbehandelter Zellen. Alle TNTs, sowohl unbehandelter als auch mit Stressfaktoren behandelter ARPE-19-Zellen, sind aus Aktin aufgebaut. Jedoch ließ sich kein Tubulin nachweisen. Nach Zugabe von Aktinpolymerisationshemmern waren keine TNTs nachweisbar, was beweist, dass F-Aktin essentieller Bestandteil von TNTs zwischen ARPE-19-Zellen ist. Unter dem Einfluss von Blaulicht 470 und 405 nm bildeten sich die TNTs, wie auch bei unbehandelten Zellen, durch ein Zusammentreffen der Zellen mit anschließendem Auseinandergleiten. Die Ursache für die verminderte Bildung an TNTs unter verschiedenen Stressfaktoren könnte in der Entstehung von oxidativem Stress durch die Ausbildung von reaktiven Sauerstoffspezies (ROS) begründet sein. So können zum Beispiel die unter Blaulicht- und Glyoxalexposition entstehenden ROS sowie H2O2, als eine Hauptform der ROS, die Zellfunktion durch Inaktivierung zellulärer Proteine beeinflussen sowie eine direkte Oxidation an Aktin hervorrufen mit folglicher Aktinnetzwerkzerstörung und Hemmung der Aktinpolymerisation (Chen, 1993; Ballinger et al., 1999; Thornalley et al., 1999; Valen et al., 1999; Dalle-Donne et al., 2002; Nilsson et al., 2003; Shangari und O'Brien, 2004; Zhu et al., 2005; Knels, Worm et al. 2008; Roehlecke et al., 2009). Die verminderte Aktinpolymerisation, aber auch die Zerreißungen der TNTs durch Veränderungen am Aktinzytoskelett sowie an den Membranen könnten zu einer verringerten TNT-Bildung führen (Valen et al., 1999; Dalle-Donne et al., 2002; Reber et al., 2002; Zhu et al., 2005; Knels et al., 2008). Auch eine Hemmung des Zellwachstums unter oxidativen Stressbedingungen sowie unter Nährstoffmangel durch Serumentzug könnte mit einer verminderten TNT-Bildung einhergehen. Wir haben in unserer Untersuchung gezeigt, dass es durch verschiedene Stresseinflüsse zu einer Reduktion der TNTs zwischen ARPE-19-Zellen kommt. Es ist denkbar, dass solche TNTs in vivo zwischen RPE- und Photorezeptorzellen ausgebildet werden, wo sie nützliches oder recycelbares Material zwischen Zellen austauschen (Wang et al., 2011; Wittig et al., 2012). Bei Zerstörung der TNTs durch zum Beispiel oxidative Faktoren könnte es zu einer Verringerung des Informationsaustausches kommen. Es ist möglich, dass durch die Minderversorgung die Zellen absterben, sowohl RPE- als auch Photorezeptorzellen. Dies könnte ein weiterer möglicher Ursachenansatz in der Entstehung der altersabhängigen Makuladegeneration sein, welche als Erkrankungserscheinung den Untergang der RPEZellen und damit sekundär der Photorezeptorzellen aufweist.

No description available.

No description available.

Purpose: To investigate species differences in the distribution and localization of alpha B-crystallin (ABC) in the normal retina and optic nerve head region, and to describe changes during outer and inner retina degeneration. Material and methods: Animals studied included mice, rats, cats, pigs, cows, and monkeys. Sections of the optic nerve and central retina were labeled with antibodies against ABC and glial fibrillary acidic protein (GFAP). Results: ABC was located in astrocytes and Muller cells with different intensities. During outer retina degeneration (dystrophic rat and Abyssinian cat), only late stages showed an increase in ABC in the retina and optic nerve head. Inner retina degeneration in the glaucoma mouse model showed no increase of ABC. In the monkey glaucoma model, only the innermost layer of the optic nerve head showed increased labeling for ABC. Conclusions: The distribution of ABC is species dependent and is (excluding the mouse) present in the nerve fiber layer of the retina and in the optic nerve head (localization of astrocytes). Chronic retinal degeneration does not necessarily lead to an over-expression of ABC. While in outer retinal degeneration induction was predominantly present in late stages, pressure-induced glaucoma led to a specific increase in ABC already in early stages indicating a local stress-response in this region.

In nature, cells are not randomly clustered to form tissues. The tissue is a more complicated system with functions that go beyond what any single cell type could accomplish. While studying single-cell mechanics and dynamics is relevant from an investigative point of view, this approach loses, or fail to gather information about the tissue. The tissue investigated in this study is the neurosensory retina which seeing as extension of the brain is a very convenient model for the central nervous system due to its accessibility. The retina is constantly subjected to different mechanical stresses from development to adulthood. Although the majority of the phenomena where mechanical stresses are involved are well-studied, the mechanics behind them is not well understood. However, knowledge about the ability of the retina to adjust to mechanical stresses is essential, for example, for improving retinal surgery. Establishing a method to mechanically probe the retina is a challenge due to the extremely delicate nature of this multilayered neural tissue and to the short-time survival ex vivo. The organotypic tissue culture is a powerful tool because it allows to maintain with high accuracy the complex multicellular anatomy and the microenvironment of the original tissue. One of the limitations of the organotypic culture techniques has been until recently due to the ability to use only post-natal/juvenile tissues for long-term culture. The importance of using adult tissue is incontestable when the investigation focuses on age-related pathologies such as vitreous shrinkage or macula degeneration. In this work, TiO2 nanotube arrays are presented as the innovative substrate for long-term organotypic culture of adult neural tissue. The retinal whole-mount of adult guinea pig and the brain slices of adult mouse were cultures for 14 days without showing any sign of edema or swelling. Furthermore, in order to study the behavior of the retinal tissue under shear stress new set-ups were designed. For the first time, the behavior of the retinal layers were observed showing that the retina does not act as an homogeneous material in response to an applied stress. The methods developed here can be used for future quantitative studies, to provide an exact knowledge of retinal biomechanics which will help retinal surgeons to optimize their methods.

[Truncated abstract] Developmentally, the rodent retinocollicular projection is often thought of as a homogenous projection of retinal ganglion cell (RGC) axons, however the extensive period of RGC neurogenesis and sequential arrival of their axons into central targets such as the superior colliulus (SC) suggests otherwise. RGC axons are already present in the developing SC at embryonic (E) day 16.5-17. RGCs born on E15 have innervated the SC by birth, whereas axons derived from RGCs that are born last (E19) do not grow into the SC until postnatal (P) days 4-6 (Dallimore et al., 2002). These observations may go someway to explaining why, after SC lesions in rats at P2, there is greater growth distal to the lesion site compared to lesions made at P6 (Tan and Harvey, 1997b). It may be that the post lesion growth is simply de novo growth of axons from late-born RGCs rather than regeneration of pre-existing, injured axons. Early and late cohorts of growing RGC axons presumably encounter different developmental terrains as they grow from retina to central targets, possibly resulting in differences in developmental milestones and growth potentials. There may also be differences in guidance cues, further suggesting that gene expression in early vs late born RGCs may differ. To examine differences between early (E15) and late (E19) born RGCs during development, the time-course and extent of programmed RGC death in normal rat pups, and RGC death following the removal of target-derived trophic factors, was assessed. ... On the other hand, LCM captured GCL analysed for gene expression at P0 and P7 revealed decreases in AKT, Math5, Notch1, c-jun, DCC, Arginase-1 mRNA levels and a considerable decrease in GAP-43 expression. It is not surprising to see differences in gene expression between whole eye and the more specific GCL samples, as the cells in all layers of the retina have very different functions and different developmental profiles. It is important to note decreases in mRNA expression in the GCL for a number of the genes analysed at P0 and P7, reflecting cessation of RGC death and completion of axonal growth into central visual targets. I also examined at the protein level expression of DCC, Arginase1, c-Jun and Bcl-2 at birth (P0) in BrdU labeled RGCs born on E15 or E19. When comparing the percentage of double labelled cells compared to the total number of cells expressing each protein, Bcl-2, c-Jun and Arg1 were expressed more in E15 RGCs (22.90%, 72.71%, and 16.44% respectively in E15 RGCs, compared with 0.52%, 13.17% and 3.59% in E19 RGCs). In contrast, DCC was expressed more at birth in E19 RGCs (18.05% in E19 RGCs compared with 9.23% in E15 RGCs). This shows there is clearly a difference in the expression of proteins in the two cohorts of RGCs, which is consistent with PCR data and with their growth state as their axons encounter the changes in the newborn brain. The overall findings of this research suggest that seemingly homogenous populations of neurons are quite different in their developmental profile and in their response to injury. This work may provide new ways of determining better strategies for CNS repair and the most effective way of targeting cells for regeneration and survival.

No description available.

Made available in DSpace on 2015-07-22T20:49:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-28 / O objetivo deste trabalho é avaliar as anormalidades da esclera, coroide e retina de coelhos induzidas pela dieta hipercolesterolêmica, além da possibilidade de prevenção dessas anormalidades com administração sistêmica de rosiglitazona. Para isto, 54 coelhos new zealand foram distribuídos em quatro grupos: grupo-controle (GC) recebeu dieta normal; grupo 1 recebeu dieta hipercolesterolêmica; grupo 2 recebeu dieta hipercolesterolêmica associada à administração diária de 3 mg de rosiglitazona a partir do 14º dia do início do experimento; e grupo 3 recebeu dieta hipercolesterolêmica associada à administração diária de 3 mg de rosiglitazona desde o início do experimento. Os coelhos foram pesados e submetidos à dosagem sérica de colesterol total, triglicerídeos, high density lipoprotein (HDL) colesterol e glicemia de jejum no início do experimento, no 14º dia e no momento da eutanásia (42º dia). A esclera e coroide foram submetidas à análise histológica e histomorfométrica. A retina foi submetida à análise imuno-histoquímica com o anticorpo monoclonal anticalretinina (CR) e anticorpo anti-glial fibrillary acidic protein (GFAP). Quando positivo para o marcador anticalretinina, duas análises quantitativas foram realizadas. Na primeira, foram contadas todas as células ganglionares imunorreativas. Na segunda, todas as células e elementos celulares imunorreativos foram avaliados pelo exame de morfometria de cores. Os dados foram analisados pelo teste nãoparamétrico de Kruskal-Wallis e teste de Shapiro-Wilks-Testand. Valores abaixo de 0,05 foram considerados estatisticamente significantes. Os resultados referentes ao peso demonstraram significativo aumento nos grupos 1 e 3 em relação ao GC no 14º dia (p<0,009), enquanto no 42º dia os grupos 1, 2 e 3 apresentaram representativamente mais peso que o GC (p<0,023). Quanto às variáveis laboratoriais, destacaram-se o aumento significativo da glicose e colesterol total de G1 em relação ao controle (p<0,001), assim como o acentuado aumento da HDL no G3 em relação aos demais grupos (p<0,001), no 14º dia. A HDL manteve-se expressivamente elevada no G3 em relação aos demais grupos no momento da eutanásia (p<0,001). À análise histomorfométrica da esclera e coroide obteve-se normalidade do GC. Por outro lado, o G1 mostrou marcante aumento da espessura da esclera e coroide em relação ao GC (p=0,008), enquanto que no G3 houve espessamento de esclera e coroide menor que no G1 (p=0,048). Elevado número de histiócitos foi observado na parede escleral do grupo submetido à dieta hipercolesterolêmica (G1), seguido de forma decrescente por G2, G3 e GC. A análise imuno-histoquímica da retina com o anticorpo monoclonal anticalretinina ressaltou número mais alto de células ganglionares imunorreativas no G1 que no G3 (p=0,002). O exame de morfometria de cores revelou significativa imunorreatividade das células e elementos celulares do G1 em relação aos outros grupos (p<0,001). Nesta análise evidenciou-se também acentuada imunorreatividade das células e elementos celulares de G2 e G3 em relação ao GC (p≤0,002). GFAP foi negativo em todos os grupos. Neste modelo, os achados permitem concluir que a hipercolesterolemia provoca anormalidades precoces histomorfométricas e imuno-histoquímicas do complexo esclerocoriorretiniano; e a ativação dos receptores do PPAR gama-ocular, a partir da dieta oral de rosiglitazona, foi efetiva em atenuar tais anormalidades nessas estruturas. / The purpose of this study is to evaluate scleral, choroid and retinal abnormalities in rabbits induced by a hypercholesterolemic diet and the prevention of these abnormalities after oral administration of rosiglitazone in rabbits. Fifty-four new zealand rabbits were divided into four groups: the control group (CG) was fed a normal diet; group 1 G1), a hypercholesterolemic diet; group 2 (G2) a hypercholesterolemic diet associated with daily administration of 3 mg of rosiglitazone from day 14 after the beginning of the diet; and group 3 G3), a hypercholesterolemic diet associated with daily administration of 3 mg of rosiglitazone since the beginning of the experiment. The rabbits were weighed and underwent the following examinations: seric dosages of total cholesterol, triglycerides, cholesterol HDL, and fasting glycemia at the beginning of the experiment, on the 14th day and on the 42nd, the euthanasia day. The sclera and choroid underwent histologic and histomorphometric analyses and the retina underwent immunohistochemical analysis with anti-calretinin (CR) and anti-glial fibrillary acidic protein (GFAP) antibody. When positive for the anti-calretinin marker, two quantitative analyses were performed. In the first analysis, all immunoreactive ganglion cells were counted. In the second analysis, all immunoreactive cells and cell elements were studied with the color morphometry method. The data were evaluated using the nonparametric Kruskal-Wallis and the Shapiro – Wilk tests. Values of p<0.05 were considered statistically significant. The results obtained showed a significant weight increase in Groups 1 and 3 in relation to CG on Day 14 (p<0.009). Additionally, a significant weight increase was observed in G1, G2 and G3 in relation to CG on Day 42 (p<0.023). The lab results showed a significant increase in glucose and total cholesterol in G1 in relation to CG (p<0.001) on Day 14, as well as a significant HDL increase in G3, when compared with the other groups (p<0.001) on Day 14. HDL in G3 was significantly high when compared to the other groups, on the euthanasia day (p<0.001). The results obtained regarding weight showed a significant increase in Groups 1, 2 and 3 in relation to CG on Day 14 (p<0.01) and Day 42 (p<0.02). The lab results showed a significant increase in glucose and total cholesterol in Groups 1, 2 and 3 in relation to CG (p<0.01) on Day 14, as well as a significant increase in HDL in G3 when compared with the other groups, on euthanasia day (p<0.01). The histomorphometric analysis of CG sclera and choroid presented normal results. Conversely, G1 showed a significant increase in sclera and choroid thickness in relation to CG (p= 0,008), whereas G3 showed thickness lower than in G1 (p=0,048). A larger number of histiocytes were observed on the scleral wall of the group that was fed the hypercholesterolemic diet (G1), followed, in a descending order, by groups 2 and 3, and the control group. The immunohistochemical analysis of the retina with the anti-calretinin monoclonal antibody showed that G1 presented a larger number of immunoreactive ganglion cells than G3 (p = 0.002). The color morphometry showed significant immunoreactivity of G1 cells and cell elements when compared with the other groups (p<0.001). A significant immunoreactivity of G2 and G3 cells and cell elements in relation to CG was also observed (p<0.002). GFAP results were negative in all groups. The findings of this proposed study model suggest that hypercholesterolemia induces early histomorphometric and immunohistochemical abnormalities in the sclerochorioretinal complex and that the activation of PPAR gamma in ocular cells attenuated these abnormalities with the administration of the oral rosiglitazone diet. / TEDE / BV UNIFESP: Teses e dissertações