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| Author(s): |
Gabriela Lourençon Ioshimoto
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Psicologia (IP/SBD) |
| Defense date: | 2015-10-08 |
| Examining board members: |
Dora Selma Fix Ventura;
Dania Emi Hamassaki;
Christina Joselevitch;
André Márcio Vieira Messias;
Fernando Allan de Farias Rocha
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| Advisor: | Dora Selma Fix Ventura; Francisco Max Damico |
| Abstract | |
Chronic uveitis are generally intraocular inflammations and the major cause of blindness in the world. The corticosteroids are the drugs of first choice for the treatment of autoimmune uveitis, but is often need for use of other immunosupressive drugs. However, both immunossuppressants ans corticosteroids are associated with serious side effects that may lead to the need for dose reduction or dicontinuation of the drug. As an alternative to traditional drug delivery (systemic and topical) and to reduce the side effects, this study aims 1) to verify the viability of intravitreal MPA implant in the control rabbits, 2) to reproduce the experimental autoimmune uveitis model (EAU) induced with M. tuberculosis and 3) to evaluate the therapeutic effects of MPA biodegradable implant in EAU rabbits through ERG and clinical longitudinal analysis and morphological analyzes after 50 days. The results confirmed the viability and tolerance of the MPA intravitreal implant. The EAU model developed a self-limiting anterior uveitis, an inflammation peak at 21 days indicated by the increase in the anterior chamber cells, flare and conjunctival hyperemia. The ERG showed that this model present a decrease of the amplitudes and an increase of the implicit times. Our clinical results showed that the MPA implant decreased the uveitis degree during the peak of inflammation reducing conjunctival hyperemia, the presence of cells in the anterior chamber and the presence of flare. However, after 35 days of treatment, we observed retinal detachment in 60% of animals. Electroretinography results also showed a reduction of inflammation through the recovery of the scotopic b-waves amplitude and implicit time of the photopic responses of both a- and b-waves for the treated group. After 50 days of treatment, immunohistochemistry revealed that the activation of glial cells had become smaller without, indicating a reduction of the inflammatory process. With these results, we concluded that MPA intravitreal implant supressed the inflammation during the peak of inflammationin a rabbit model of uveitis. And besides reducing the clinical signs of disease, the drug recovered the photoreceptors, ON bipolar and Müller cells functions that have been altered by inflammation. Our results suggest thatthe therapeutic effect of MPA occurs when the drug concentration approaches 700 ng / mL in the vitreous (AU) | |
| FAPESP's process: | 12/05298-5 - THERAPEUTIC STUDY OF MPA INTRAVITREAL IMPLANT IN EXPERIMENTAL AUTOIMMUNE UVEITIS |
| Grantee: | Gabriela Lourençon Ioshimoto |
| Support Opportunities: | Scholarships in Brazil - Doctorate |