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

Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years. Environmental and genetic risk-factors contribute to the development of AMD. An AMD-risk locus on chromosome 10q26 spans two genes, ARMS2 and HTRA1, and controversy exists as to which variants are responsible for increased risk of disease. Recent work suggests that HTRA1 expression levels are significantly increased in carriers of the risk haplotype associated with AMD. However, relatively little is known about the interactions, substrate specificity and roles in disease played by this secreted serine protease. This thesis aims to elucidate the potential role played by HTRA1 in AMD pathogenesis. A combination of tandem affinity purification (TAP) and yeast two-hybrid techniques was used to identify interacting partners of HTRA1. A number of proteins, with diverse roles in the alternative complement pathway, cell signaling, cell-matrix interactions, inflammation, angiogenesis and fibrosis, were identified. These are attractive candidates for further study as such processes are disturbed in AMD, implicating HTRA1 and its binding partners in disease development. One interacting partner, Complement Factor D (CFD), is a key activator in the alternative complement pathway. CFD, a 24 kDa serine protease, is expressed as an inactive zymogen, from which a signal peptide and activation peptide are cleaved before release of the mature, active protein into the circulation. In vitro studies show that CFD interacts with, and can be a substrate for, HTRA1. The interacting domain between the two proteins is localised to a region of 30 amino acids at the N-terminal end of proCFD. The 5 amino acid pro-peptide of CFD appears to be both necessary and sufficient for proteolysis of CFD by HTRA1. Investigation of the functional relevance of the interaction between HTRA1 and CFD shows that proCFD is cleaved by HTRA1, whilst mature CFD is not subjected to proteolysis. HTRA1-mediated cleavage of CFD forms an active protease, leading to activation of factor B in the alternative complement pathway in in vitro assays. Furthermore, a normal complement response is restored to CFD-depleted serum by addition of proCFD activated by HTRA1. Thus, an HTRA1- mediated increase in alternative complement pathway activity may explain a proportion of the AMD-risk attributed to the chr10q26 locus. Genetic and protein-based approaches were used to study the potential role of CFD in AMD pathogenesis, independent of an interaction with HTRA1. An intronic SNP, rs3826945, was significantly associated with increased risk of AMD in two British case-control cohorts, and in a combined meta-analysis with 4 additional cohorts from North America and Europe (p-value = 0.032, Odds Ratio = 1.112 in 4765 cases and 2693 controls). Assessment of copy number variation and sequencing of CFD did not identify any functional variants which may explain the association with disease. However, plasma levels of CFD were measured by ELISA in 751 AMD cases and 474 controls, and were found to be significantly elevated in AMD cases compared to controls (p-value = 0.00025). This further implicates complement activation in AMD pathogenesis, and makes CFD an attractive candidate for therapeutic intervention. An alteration in the level of activated CFD, possibly mediated via an interaction with HTRA1, either at the systemic or local tissue level, may play a role in disease development and progression.

Made available in DSpace on 2014-06-12T16:25:36Z (GMT). No. of bitstreams: 2 arquivo3196_1.pdf: 1609060 bytes, checksum: 56d061c007d949c235169a3a4808b5b6 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / Objetivo: Avaliar a microbiota bacteriana da conjuntiva e sua sensibilidade aos antibióticos em portadores de degeneração macular relacionada à idade (DMRI) exsudativa, comparando com a de portadores de catarata. Métodos: Realizou-se estudo prospectivo, observacional, analítico, com corte transversal em duas populações de estudo. Foram constituídos dois grupos: grupo I (DMRI exsudativa ativa com indicação de injeção intravítrea de bevacizumab) com 16 olhos de 16 pacientes (oito do sexo masculino e oito do feminino) com média de idades de 71,3±9,9 anos; grupo II (catarata em pré-operatório para cirurgia) com 27 olhos de 27 pacientes (nove do sexo masculino e 18 do feminino) com média de idades de 67,6±7,9 anos. Os grupos foram homogêneos em relação à idade (p=0,180) e ao sexo (p=0,280). Foi realizada coleta de secreção do fundo de saco inferior da conjuntiva, através de swab, e imediatamente colocado em tubo contendo meio líquido BHI (brain heart infusion). As amostras foram processadas conforme técnicas laboratoriais padrão e realizado antibiograma de cada colônia isolada. Resultados: Houve crescimento de 17 colônias bacterianas no grupo I, com um olho não apresentando crescimento e 30 colônias no grupo II. Houve maior frequência de bactérias Gram positivas nos dois grupos: 14/17 colônias (82,3%) no grupo I e 29/30 colônias (96,7%) no grupo II, com predomínio de Staphylococcus aureus em ambos os grupos, com oito amostras (47,1%) e 17 (56,7%), respectivamente. Staphylococcus coagulase negativa foi a segunda bactéria mais identificada, com 23,5% no grupo I e 20,0% no grupo II. Nenhuma diferença de freqüência entre os grupos alcançou significância estatística. Não foi observada diferença estatisticamente significante na sensibilidade das bactérias aos antibióticos testados entre os dois grupos, entretanto houve tendência para maior resistência à oxacilina nos portadores de DMRI (p=0,081). Conclusão: Não houve diferença na distribuição das bactérias e sensibilidade aos antibióticos da microbiota conjuntival em portadores de DMRI exsudativa, comparada com a de catarata

Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2017-09-26T15:36:47Z No. of bitstreams: 2 Dissertação - Letícia Pinto Coelho Jorge - 2017.pdf: 7825738 bytes, checksum: 4eca5b3a59512770f7384ddd353ddb59 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-09-27T11:21:13Z (GMT) No. of bitstreams: 2 Dissertação - Letícia Pinto Coelho Jorge - 2017.pdf: 7825738 bytes, checksum: 4eca5b3a59512770f7384ddd353ddb59 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-09-27T11:21:13Z (GMT). No. of bitstreams: 2 Dissertação - Letícia Pinto Coelho Jorge - 2017.pdf: 7825738 bytes, checksum: 4eca5b3a59512770f7384ddd353ddb59 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-09-19 / Macula lutea is the region of the retina where the yellow pigments lutein and zeaxanthin are concentrated. Oxidative damage seems to be an important factor for exacerbation of several retinal diseases, such as age-related macular degeneration, and a protective role of macular pigment has been postulated. The quantitative study of macular pigment and its distribution are possible through the determination of macular pigment optical density (MPOD). The objective of this study was to determine the mean MPOD value in a sample of the Brazilian population and to evaluate the influence of sex, age, ethnicity, smoking history and refractive status on MPOD values in this sample. A cross-sectional study was performed. Forty-two healthy patients had both eyes photographed using Visucam 500 (Carl Zeiss Meditec, Jena, Germany) in combination with the MPOD module. Four variables were obtained: maximum MPOD, mean MPOD, MPOD volume and MPOD area. Demographic data and life habits were collected. The mean MPOD value in the studied population was 0.13 density unit ± 0.02. MPOD values were not influenced by gender, smoking history or refraction. MPOD values were significantly higher among black patients when compared to caucasians. There was a positive but low correlation between mean MPOD and age. / A mácula lútea é a região da retina onde se concentram os pigmentos amarelos luteína e zeaxantina. Acredita-se que eles sejam um fator de proteção para doenças atribuídas ao estresse oxidativo, como degeneração macular relacionada à idade. O estudo quantitativo do pigmento macular e sua distribuição são possíveis por meio da medida da densidade óptica de pigmento macular (MPOD). O objetivo deste trabalho foi determinar o valor médio de MPOD em uma amostra da população brasileira e avaliar a influência dos fatores sexo, idade, etnia, histórico de tabagismo e status refracional nos valores de MPOD nesta amostra. Foi realizado estudo tipo corte transversal. Quarenta e dois pacientes saudáveis tiveram ambos os olhos fotografados utilizando o Visucam 500 (Carl Zeiss Meditec, Jena, Alemanha) em combinação com o módulo MPOD. Quatro variáveis foram obtidas: MPOD máxima, MPOD média, volume de MPOD e área de MPOD. Foram colhidos dados demográficos e hábitos de vida. O valor médio de MPOD nesta amostra da população brasileira foi de 0,13 unidade de densidade ± 0,02. Os valores de MPOD não foram influenciados pelo sexo, histórico de tabagismo ou refração. Os valores de MPOD foram significativamente maiores entre os pacientes negros, quando comparados aos brancos. Encontrou-se uma correlação positiva, porém baixa, entre o valor de MPOD médio e a idade.

Made available in DSpace on 2014-06-12T18:27:29Z (GMT). No. of bitstreams: 2 arquivo1004_1.pdf: 1251472 bytes, checksum: 1f6e464692ea89b8cd077af78f9fa70b (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2010 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / A injeção intravítrea representa um dos maiores desafios na terapêutica oftalmológica atual para o tratamento da degeneração macular relacionada à idade, na forma exsudativa, embora as injeções intravítreas possam levar a endoftalmite póscirurgica, onde a fonte pricipal é a microbiota conjuntival. Objetivos: descrever a microbiota conjuntival bacteriana e fúngica de portadores de degeneração macular relacionada à idade no peri-operatório com uso de injeção intravítrea de antiangiogênico em um esquema terapêutico trimestral. Métodos: foi realizado um estudo de série de casos com 35 pacientes submetidos a injeção intravítrea de antiangiogênico para o tratamento de DMRI e 30 pacientes controles sadios, na Fundação Altino Ventura-PE. O material da conjuntiva foi coletado em 4 momentos: (t0) antes da primeira aplicação de antiangiogênico; (t1) após uso tópico de 3 dias de antibiótico; (t2) antes da terceira aplicação de antiangiogênico e (t3) no retorno de 30 dias após término, para o grupo DMRI. Com relação ao grupo controle, foi feita apenas uma coleta para o islomento bacteriano e fúngico, correspondente a t0. A coleta foi através de swab no fundo de saco conjuntival inferior, e colocado em meio BHI.O processo de investigação microbiológica seguia as seguintes etapas:bacterioscopia, cultura e antibiograma. Resultados: para o grupo DMRI, o houve crescimento positivo das culturas para os momentos t0, t1, t2 e t3, cujos percentuais foram respectivamente de 91,4%; 28,6%; 74,3% e 94,3%. Para o grupo controle, foi realizada a cultura da microbiota apenas no momento t0, evidenciando-se um percentual de 93,3% de culturas positivas. Para ambos os grupos houve maior freqüência de bactérias Gram-positivas em todos momentos, prevalecendo às espécies Staphyloccocus aureus e Staphyloccocus coagulase negativo. Os fungos mais frequentemente isolados Aspergillus sp e Penicillium sp para ambos grupos.Conclusão: não houve diferença na distribuição dos micro-organismos isolados na conjuntiva dos portadores de DMRI, comparada aos pacientes controles

Both proliferative diabetic retinopathy and exudative age-related macular degeneration are major causes of blindness which are caused by growth of defective, leaky and tortuous blood vessels in the retina. Hypoxia is implicated in triggering both of these diseases and results in induction of HIF-1alpha transcription factor in addition to the angiogenic factor VEGF. Müller cells are the major glial cell in the retina and they contribute to neovascularization in hypoxic regions of the retina through eliciting secretion of growth factors, cytokines and angiogenic factors. As Müller cells span the breadth of the retina they can secrete angiostatic factors as well as neuroprotective trophic factors, the Müller cell is a valuable cell type for targeting by potential new gene therapies. The current investigation tests the hypoxia responsiveness of an AAV vector containing a hybrid hypoxia response element together with a GFAP promoter, and this vector encodes the angiostatic protein decorin, a well characterized multi-receptor tyrosine kinase inhibitor. Decorin may have advantages over other key angiostatic factors such as endostatin or angiostatin by virtue of its multiple anti-angiogenic signaling modalities. We employed Q-RT-PCR to evaluate the cell specificity and hypoxia responsiveness of an AAV-Vector termed AAV-REG-Decorin containing a hybrid HRE and GFAP promoter driving expression of the decorin transgene. The vector also contains a silencer element between the HRE and the GFAP domains to enable low basal expression in normoxia as well as high level inducibility in hypoxia. AAV-REGDecorin was found to elicit high level expression of decorin mRNA in hypoxia with greater than 9 – fold induction of the transgene in hypoxic conditions in astrocytes by comparison to normoxic astrocytes. AAV-REG-Decorin showed low levels of transgene expression by comparison to the positive control vector AAV-CMV -decorin containing the ubiquitously active CMV-promoter. The expression levels of decorin mRNA from AAV-REG-Decorin and from AAV-GFAP-Decorin were low in the PC12 neuronal cell model and in the ARPE19 line of retinal pigment epithelial cells with respect to those of AAV-CMV-decorin and no induction of Decorin mRNA was found with AAV-REGDecorin in these two control cell lines. Our novel gene therapy vector will serve as a platform for testing efficacy in rodent disease models (OIR and laser induced choroidal neovascularization) for assessment of the benefits of tightly regulated antiangiogenic gene therapy eliciting decorin transgene expression, both in terms of timing and the cellular source of production, during the progression of the retinal pathophysiology. / Includes bibliography. / Dissertation (PhD)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

No / Purpose To determine the usefulness of a battery of potential vision tests (PVTs) including potential acuity meter (PAM), laser interferometer (LI), critical flicker/fusion frequency (CFF), superilluminated pinhole at distance (SPHd) and near (SPHn), and optimal reading speed (ORS) by their independence of the effects of cataracts and sensitivity to macular disease (MD). Setting Department of Optometry, University of Bradford, Bradford and Leeds General Infirmary, Leeds, United Kingdom. Methods Potential vision test measurements were determined in 76 patients with age-related cataract and no other eye disease, 52 patients with MD and clear ocular media, and 28 patients with normal, healthy eyes. Results Potential vision tests were independent of the degrading effects of cataract up to a visual acuity (VA) level of 20/200 or worse (CFF), 20/125 (ORS and SPH), and 20/40 (PAM and LI). A high degree of association was found between PVT scores and distance VA in the MD group for SPHd (r2 = 0.93), SPHn (r2 = 0.89), and PAM (r2 = 0.71). A moderate correlation was found for LI (r2 = 0.55), CFF (r2 = 0.50), and ORS (r2 = 0.45). Conclusions Potential acuity meter and LI showed very limited independence to moderate/dense cataracts and inaccurate predictions in patients with MD. Superilluminated pinhole was relatively unaffected by moderate/dense cataract and yet provided accurate predictions in the presence of MD and clear ocular media. Critical flicker/fusion frequency showed the greatest ability to bypass cataracts, although its ability to predict VA in patients with early MD was limited. The ORS was relatively unaffected by moderate/dense cataract, but its poor ability to predict VA in MD may limit its clinical suitability as a PVT.

C1QTNF5 is a 25kDa short chain collagen of unknown function which is mutated in late-onset retinal macular degeneration (L-ORMD). L-ORMD is an autosomal dominant disease characterised by sub-retinal pigment epithelial deposits leading to photoreceptor death and visual loss and shows several similarities to age-related macular degeneration (AMD). A Tyr402His polymorphism in complement factor H (CFH), a regulatory protein in the innate immune system, has been associated with increased risk of AMD. C1QTNF5 and CFH are both expressed and secreted by the retinal pigment epithelium (RPE) which supports photoreceptors and is responsible for phagocytosis of shed rod photoreceptor outer segments (ROS). The properties of the normal C1QTNF5 and disease-associated Ser163Arg mutation were examined in detail, including protein characterisation, cellular processing and function. Recombinant wild type and mutant C1QTNF5 were produced and their multimerisation and solubility functions compared. Both proteins were found to be soluble and to form similar multimeric species which were resistant to reducing conditions, as seen in other short chain collagens. Due to the similarities between LORMD and AMD, a proposed interaction between C1QTNF5 and CFH was investigated. CFH is composed of 20 short consensus repeats (SCR) and interactions were confirmed between C1QTNF5 and both CFH and SCR modules 7-8 and 19-20. CFH showed a greater affinity for mutant C1QTNF5 compared with wild type on the basis of surface plasmon resonance assays. Stably transfected RPE-derived cell lines were created which expressed either wild type or mutant C1QTNF5. Both proteins were found to be secreted and showed similar cellular processing with no evidence of aggregation or retention of the mutant protein within the endoplasmic reticulum. In order to investigate C1QTNF5 function, phagocytosis of ROS by the stably transfected cell lines was carried out. Cells expressing wild type C1QTNF5 showed greater ROS phagocytosis compared with mutant C1QTNF5-expressing or untransfected cells. Addition of anti-C1QTNF5 antibody increased ROS phagocytosis further. In summary, it is proposed that wild type and mutant C1QTNF5 are secreted by the RPE where they interact with CFH. C1QTNF5 is also shown to have a role in ROS phagocytosis, with mutation in C1QTNF5 affecting phagocytosis efficiency, which may contribute to sub-RPE deposit formation. The results suggest that CFH may also be involved in this process, suggesting a common pathogenic pathway between L-ORMD and AMD.

Face à la limite de la littérature sur l’impact de l’environnement notamment alimentaire dans le vieillissement oculaire liée en partie aux manques de données en population générale particulièrement la plus âgée en France, nous nous sommes intéressés dans un premier temps, aux relations entre l’alimentation, les xanthophylles plasmatiques et le pigment maculaire puis sa distribution spatiale et dans un second temps, au profil des acides gras et les signes de sécheresse oculaire chez les 1153 participants de l’étude Montrachet.Dans un premier temps, nous avons mis en évidence une augmentation de la concentration plasmatique de lutéine et zéaxanthine chez les personnes consommant fréquemment des courges et courgettes et ainsi, une augmentation de la densité optique du pigment maculaire chez les personnes âgées non-fumeurs ayant une concentration plasmatique élevée en lutéine. De plus, nous avons fourni des valeurs du pigment maculaires qui pourraient servir de référence en population générale pour des études épidémiologiques. Nos résultats sont très cohérents avec ceux des autres études épidémiologiques même si notre population est en moyenne plus âgée. Par ailleurs, nous avons montré que les signes de la sécheresse oculaire sont plus fréquents chez les personnes âgées ayant des concentrations plasmatiques faibles en acides gras polyinsaturés et saturés. Ainsi, nos résultats apportent des éléments nouveaux dans l’implication des acides gras dans le processus de la sécheresse oculaire.Enfin, ces travaux de thèse, viennent enrichir la littérature relative au pigment maculaire, sa densité, sa répartition spatiale et ses déterminants ainsi que les déterminants de la sécheresse oculaire. Cependant, compte tenu de caractère transversal de nos études, ces résultats permettent seulement d’émettre des hypothèses qui seront confirmées à l’aide d’études longitudinales et pourraient contribuer à conforter l’intérêt des interventions reposant sur des supplémentation en caroténoïdes xanthophylles. / Given the limits of the literature on the environmental nutritional impact in ocular aging witch is partially due to the lack of data in general population notably in French elderly, first, we were interested in the relationships of diet, plasma xanthophylls and macular pigment optical density as well as its spatial distribution and second of plasma fatty acids and dry eye disease signs in the 1153 Montrachet study participants.Firstly, we reported the high consumption of squash, the high plasma lutein and zeaxanthin levels and also the high plasma lutein level, the high macular pigment optical density level in nonsmokers subjects. In addition, the macular pigment values we provided in the study could be used as reference in population based study. Our results are very consistent with those found in other epidemiological studies even though our population is on average older. Secondly, we have shown that dry eye disease signs are more frequent in elderly subjects with low plasma polyunsaturated and saturated fatty acids level. Thus, our results provide new elements in the involvement of fatty acids in the process of dry eye disease.Finally, this work enriches the literature on macular pigment, its density, as well as its spatial distribution and its determinants as well as the determinants of dry eye disease. However, given the transversal nature of our studies, these results make only possible to formulate hypotheses that will be confirmed with longitudinal studies and could reinforce the interest of interventions based xanthophylls carotenoids supplementation in elderly.

No description available.