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Background Fibroblasts found in keloid tissues are known to present an altered sensitivity to microenvironmental stimuli. However, the impact of changes in extracellular matrix stiffness on phenotypes of normal fibroblasts (NFs) and keloid fibroblasts (KFs) is poorly understood. Objectives Investigation the impact of matrix stiffness on NFs and KFs mainly via detecting yes-associated protein (YAP) expression. Methods We used fibronectin-coated polyacrylamide hydrogel substrates with a range from physiological to pathological stiffness values with or without TGF-β (fibrogenic inducer). Atomic force microscopy was used to measure the stiffness of fibroblasts. Cellular mechanoresponses were screened by immunocytochemistry, Western blot and Luminex assay. Results KFs are stiffer than NFs with greater expression of α-SMA. In NFs, YAP nuclear translocation was induced by increasing matrix stiffness as well as by stimulation with TGF-β. In contrast, KFs showed higher baseline levels of nuclear YAP that was not responsive to matrix stiffness or TGF-β. TGF-β1 induced p-SMAD3 in both KFs and NFs, demonstrating the pathway was functional and not hyperactivated in KFs. Moreover, blebbistatin suppressed α-SMA expression and cellular stiffness in KFs, linking the elevated YAP signaling to keloid phenotype. Conclusions These data suggest that whilst normal skin fibroblasts respond to matrix stiffness in vitro, keloid fibroblasts have elevated activation of mechanotransduction signaling insensitive to the microenvironment. This elevated signaling appears linked to the expression of α-SMA, suggesting a direct link to disease pathogenesis. These findings suggest changes to keloid fibroblast phenotype related to mechanotransduction contribute to disease and may be a useful therapeutic target.

Resume Introduction Les complications ophtalmologiques de la toxoplasmose congenitale, notamment sous forme de retinochoroidite, sont particulierement redoutees. Tout enfant dont la toxoplasmose congenitale est confirmee beneficie d’un traitement systematique et d’un suivi ophtalmologique regulier, avec realisation de multiples fond d’yeux. L’objectif de notre etude est d’evaluer la prise en charge et le suivi d’une cohorte de patients alsaciens presentant une toxoplasmose congenitale, ainsi que le retentissement psychologique de cette pathologie sur les parents, a l’aide d’un questionnaire standardise. Materiel et methodes Notre etude retrospective a collige les dossiers de 35 enfants atteints de toxoplasmose congenitale, nes entre 1990 et 2011 en Alsace, suivis au niveau ophtalmologique. Un questionnaire standardise concernant le vecu des grossesses et le suivi post-natal ont ete soumis aux parents. Resultats A la naissance, une retinochoroidite a ete retrouvee chez 2 enfants sur 35, et seulement 1 enfant a developpe une chorioretinite depistee au cours du suivi ulterieur (duree de suivi entre 1 et 22 ans). Des anomalies cerebrales ont ete notees chez 3 enfants a la naissance, aucun d’entre eux n’ayant presente d’atteinte oculaire a ce jour. Un score moyen de 15 sur 23 a ete retrouve par notre questionnaire standardise, traduisant une angoisse importante vis-a-vis de la toxoplasmose congenitale. Discussion L’anxiete parentale face a la toxoplasmose congenitale, mise en evidence par notre questionnaire standardise, est manifeste. Un suivi oriente par un examen pediatrique complet a la naissance, incluant un fond d’œil, et une information precise sur les signes fonctionnels de toxoplasmose oculaire pourrait permettre d’ameliorer les modalites du depistage, sans engendrer de consequences sur la fonction visuelle.

Introduction Choroidal metastases are, with melanoma, the most frequent malignant eye neoplasms. Breast carcinoma for women and lung carcinoma for men most commonly metastasize to the eye. We report a rare case of choroidal metastasis from follicular thyroid carcinoma. Observation A 75-year-old man, with metastatic follicular thyroid carcinoma, presented a decline in visual acuity of the left eye lasting one month. The best corrected visual acuity was 3/10 in his left eye. Biomicroscopic examination of the anterior segment did not reveal anything abnormal. Funduscopic examination showed an amelanotic choroidal mass located at the posterior pole with serous retinal detachment. Tomoscintigraphy with computed tomography confirmed the thyroid origin by uptake of radioiodine in the choroidal mass. External radiotherapy was then proposed. Discussion Although it is exceptional, diagnosis of choroidal metastases should be considered in any decline in visual acuity in patients with thyroid cancer. The treatment is difficult because metastases from thyroid cancer are very poorly sensitive to radiotherapy and chemotherapy.

We report a case of a 72-year-old man who presented with bilateral panuveitis in a context of unclassified arthritis. The recurrence of uveitis associated with ear chondritis led to the diagnosis of relapsing polychondritis. Ocular symptoms are frequent in the course of relapsing polychondritis, but uveitis is a rare symptom and could compromise the visual outcome.