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Perte d'homogénéité du teint chez la femme à peau mature : approches biométrologique et cellulaire du lentigo actinique

Abstract : Based on extrinsic and intrinsic factors, skin complexion of an individual evolves in time. The Joss of its homogeneity is linked to the appearance of hyperpigmented les ions. The latters are induced by chronic sun exposure and appear with the age, as in the solar lentigo disorder. Despite its well-known characterization at the macroscopic levels, only few studies explore the skin fonctions of the solar lentigo with non-invasive tools. At the cellular and molecular levels, this lesion results from an altered process of pigmentation that is involved in the regulation of the cutaneous photo-protection. Despite the changes of the functional dialogue between the epiderrnic and derrnic layers, no study describes the functional characteristics of primary ce lis isolated from the solar lentigo. The first aim of my project consisted on a functional exploration of the solar lentigo by the use of diverse biometrological parameters. The study was carried out on a cohort of 80 women, some of them had few (grade l) and others many solar lentiges (grade 2) on their faces. Thanks to photographie measurements to determine the grade, various biometrological approaches had quantified the rates of sebum, melanin, hemoglobin, moisturizing, light reflection and the colour (L *, a*, b* and 1T A). Results of the statistical analyses revealed that the quantity of sebumdiscriminates the skin territories of the cheek and forehead, 2) the rates of melanin, hemoglobin, light reflection and the colour were differential between affected (solar lentigo) and not affected zones, within the volunteers' cheek territory, and 3) decreased rates of light reflection and hemoglobin, as well as, increased rate moisturizing, were observed within the lesional zone between both grades. Altogether, our data highlighted some of the biometrological parameters, as indicators of the skin territory, the lesional vs non lesional areas and the progression (grade 2 vs 1) of solar lentigo The second aim covered morphological and functional analyses of the solar lentigo's primary fibroblasts. This study was carried out on a cohort of 10 volunteers and two biopsies, containing the peri-lesional and lesional areas, were taken from each person. From these biopsies, human primary fibroblasts were isolated and grown. An immunofluorescence approach revealed that the fibroblasts of solar lentigo (FL) and those from adjacent healthy areas (FS) did not depict similar morphological characteristics with a differential organization of their actin cytoskeleton. Functional approaches demonstrated that FL displayed decrease of their metabolic activity, theirproliferation rates and their migration capacity, compared to FS. On the contrary, FL showed increased secretion capacity in terms of soluble factors. Our in vitro mode! of primary fibroblasts(FL/FS), which showed similarities with in vivo fibroblast's characteristics, might be considered as an appropriate cellular mode! to test active principles targeting skin complexion heterogeneity in women with mature skin. Using clinicat and translational research approaches, both objectives highlighted indicators and biomarkers of the solar lentigo. This work contributed to better understand the impact of the intrinsic and extrinsic factors in the Joss of complexion homogeneitv.
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Ranesha Goorochurn. Perte d'homogénéité du teint chez la femme à peau mature : approches biométrologique et cellulaire du lentigo actinique. Dermatologie. Université de Franche-Comté, 2016. Français. ⟨NNT : 2016BESA3002⟩. ⟨tel-01775167⟩

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