In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ.
We found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatment.
Panton-Valentine leucocidin arises from the combination of one S component (LukS-PV) with one F component (LukF-PV), whereas y-haemolysin comprises two S components (HlgA and HlgC) with one F component HlgB. The intravitreal injection of rabbit eye with the six combinations (S + F) of channel-forming leucotoxins produced by Staphylococcus aureus ATCC 49775 induced acute inflammatory reactions depending on time and doses of toxins. These reactions involved posterior chamber as well as anterior chamber and conjunctiva, eyelids and annexes. Histological examination confirmed the involvement of eye tissues and the disruption of the retinal barrier. The lesions began only 4 h after injections and persisted for at least 5 days. Clinical and biological effects of each leucotoxin were modulated by the speed of onset and intensity of inflammation and necrosis, leading to a functional classification according to the severity of the lesions (HlgA + LukF-PV > HlgA + HlgB 3 LukS-PV + HlgB 3 LukS-PV + LukF-PV > HlgC + HlgB 3 HlgC + LukF-PV). Moreover, N-acetyl p-D glucosaminidase assays on crude extracts of vitreous revealed granules and granule secretions 'from polymorphonuclear cells with levels according the above classification. These results show that channel-forming leucotoxins have a very significant inflammatory activity. As most S. aureus strains produce two or even six leucotoxins depending on the production of Panton-Valentine leucocidin, these compounds could be considered to be virulence factors.
Purpose: To determine the relationship of subfoveal choroidal thickness (ChT), refraction, and axial length in children, and evaluate the evolution of subfoveal ChT with time in myopic versus nonmyopic eyes. Methods: A total of 229 eyes of 115 children aged 2 to 16 years were included in the study. Refraction under cycloplegia, axial length, and subfoveal ChT were measured at baseline with comparative investigations at 15 months follow-up. Results: The probability for the subfoveal ChT to be thinner in myopic children compared to nonmyopic children was 0.9999. We found a relation between subfoveal ChT and axial length. At 15 months follow-up, subfoveal ChT was found to have increased in the nonmyopic eyes, but decreased in myopic patients. Conclusions: A number of studies have already shown the choroid to play an important role in the process of emmetropization. We found that ChT had a different evolution in myopic children compared to nonmyopic children. A thinner choroid may predict the onset, or progression, of myopia. Further studies, with longer follow-up, are necessary to confirm this hypothesis.
Local IL-17A production by resident cells plays a central role in the pathology of ocular toxoplasmosis. The balance between Th17 and Th1 responses (especially IFN-γ) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL-17A mAbs.
Amphotericin B is believed to interact with fungi membrane sterols to produce aggregates that form transmembrane channels. Given that collagen is one of the principal components of the cornea, it is also probable that amphotericin B may diffuse easily after cross-linking. Previous treatment with amphotericin B allowed riboflavin/UV-A effectiveness against C. albicans, Fusarium sp, and A. fumigatus. This schema might be used in the future for the treatment of keratomycosis.
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