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Experimental Uveitis (experimental + uveitis)

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Medical Sciences	100%

Selected Abstracts

Effects of intraperitoneal vitamin E, melatonin and aprotinin on leptin expression in the guinea pig eye during experimental uveitis

ACTA OPHTHALMOLOGICA, Issue 1 2006
Aysel Kükner
Abstract. Purpose:,To observe ultrastructural changes and leptin expression in the guinea pig eye during experimental uveitis (EU) and the effects of vitamin E, melatonin and aprotinin on leptin expression. Methods:,Thirty male guinea pigs were randomly classified into five groups. Group 1 was the control group. Groups 2, 3, 4 and 5 received intravitreal injections of bovine serum albumin (BSA) to induce EU. At the same time on the third day, groups 3 (EU + vitamin E), 4 (EU + melatonin) and 5 (EU + aprotinin) received intraperitoneal vitamin E (150 mg/kg), melatonin (10 mg/kg) and aprotinin (20 000 IU/kg), respectively. On the sixth day, histopathological and clinical scoring of inflammation were performed, and leptin expression was investigated in the retina, choroid, sclera, episclera and cornea, and compared. Results:,There was a remarkable increase in leptin expression in the retina, choroid, sclera and episclera in the EU group. Leptin expression in the treatment groups was similar to that in the control group. At light and electron microscopic levels, ganglion cells were oedematous and inner plexiform layer thickness had increased in the EU group retinas. Oedema was decreased in the treatment groups. Comparison of the EU and treatment groups revealed significant differences histopathologically and clinically. Conclusion:,Experimental uveitis causes an increase in leptin expression in the retina, choroid, sclera and episclera of guinea pigs. Vitamin E, melatonin and aprotinin inhibit this increase. Leptin seems to be closely related to ocular inflammation. [source]

Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004
Yvonne de Kozak
Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source]

Non-viral strategies of intra-ocular gene delivery

ACTA OPHTHALMOLOGICA, Issue 2009
F BEHAR-COHEN
Purpose Systemic anti TNF strategies are efficient to treat intraocular inflammation but require repeated injections and are associated to severe systemic side effects. Our aim was to develop a non viral gene transfer method to produce locally anti-inflammatory proteins in a sustained and minimally invasive manner in the ocular media. For this purpose, we have transformed the ciliary muscle into a bioreactor, using an electrically assisted gene transfer technique. Methods Electrotransfer (ET) of plasmids, encoding for different variants of TNF alpha soluble receptors, was performed in the ciliary muscle cells. Using toptimized conditions, soluble receptors were dosed in the ocular media up to 8 months after a single treatment. The technique has been applied in two models of intraocular inflammation: Endotoxin-Induced Uveitis (EIU) and auto immune experimental uveitis (EAU) in rats. Results When performed 8 days or 3 months before the LPS challenge, ET significantly reduced both clinical and histological signs of EIU. Particularly, iNOS, IL6 and TNF were down regulated while IL10 was upregulated. Importantly, systemic TNF alpha was not decreased demonstrating a local effect of the treatment. In EAU, ET significantly delayed the onset of EAU and deceased its severity. Similarly, a switch towards a Th2 cytokines profile was observed in the ocular media without any effect on systemic TNF alpha. Conclusion - ET is a safe and efficient non viral method to produce locally TNF alpha soluble receptors. - Local anti TNF allows for a local intraocular immunomodulation, without affecting systemic TNF. ET could therefore be used to reduce systemic side effects of anti TNF and prevent repeated injections. [source]

Progress in the appraisal and management of inflammatory CNVs

ACTA OPHTHALMOLOGICA, Issue 2009
P NERI
Purpose To review the current Literature and to describe the experience of a tertiary referral centre on the progress in the appraisal and the management of inflammatory choroidal neovascularization (CNV). Methods The current literature is reviewed and the experience of a tertiary referral centre is reported. Results CNV is a potentially severe sequela of posterior uveitis. The role of chronic inflammation has been described in experimental uveitis. For such reasons, even when biomicroscopy and fluorangiography (FA) cannot detect abnormalities, Indocyanine Green Angiography (ICGA) can show choridal anomalies. ICGA greatly improved the appraisal of the choroidal involvement, by providing reliable data for the diagnosis and for the management of inflammatory CNV. The new spectral domain optical coherence tomography (OCT) equipments can provide further informations that can be useful for a correct clinical assessment. The out-come of subfoveal CNV is poor if untreated: several procedures have been considered, even though there is lack of guidelines. Steroids, both local and systemic, are the first line therapy for non-infectious choroidal inflammation, although their long-term use can lead to unpleasant sequala, such as glaucoma and cataract. Immunesuppressive agents, lasers photocoagulation, photodynamic treatment, surgical removal and anti-Vascular Endothelial Growth Fact (VEGF) are other options. Conclusion CNV secondary to uveitis is a severe sequela leading to significant visual impairment. ICGA is mandatory in order to obtain relevant informations about the choroidal status. Several therapeutic options have been considered, but no guidelines are available at the moment. [source]

Gene transfer of disease regulated promoters during experimental autoimmune uveitis

ACTA OPHTHALMOLOGICA, Issue 2009
V ELMALEH
Purpose Adeno-associated virus (AAV) vectors have been successfully used to transfer immunosuppressive genes into the retina to prevent experimental uveitis development. Transgene expression is classically regulated by constitutive or tetracycline inducible promoters. It might be more advantageous that the control of transgene expression depends on the pathological process itself. Inflammation activates transcription factors acting on promoters containing short responsive sequences, responding, for example to nuclear factor kappa B (NF,B-RE). These responsive elements can be used to generate disease regulated promoters. Methods An AAV vector with the GFP gene under the control of a NF-kB-RE containing promoter will be injected subretinally in C57Bl6 mice. Autoimmune uveitis will be induced by adoptive transfer of IRBP specific lymphocytes. Animals will be sacrificed at different time points. GFP expression will be analysed by immunofluorescence. VCAM1, MHC II and CD45 will be analysed by immunofluorescence and used to monitor the level of retinal inflammation. Results One week after disease induction, GFP expression was found in eyes injected with this new vector. Milder GFP expression was also found in mice who did not received adoptive transfer. This background was increased a J14. Conclusion Our preliminary results suggest that disease driven GFP expression can be obtained by the use of AAV vectors containing disease regulated promoters. We still need some more times to improve our model. In the future, we plan to replace the GFP gene by an immunosuppressive gene and test if the system can be use to treat experimental uveitis. [source]