Intravitreal thalidomide ameliorates inflammation in a model of experimental uveitis induced by BCG
| Autor: | Luciana Maria Silva, Oliver Araújo Lacerda Cotta, Armando Silva-Cunha, Brenda Fernanda Moreira Castro, Sarah Pereira de Freitas Cenachi, Mayara Rodrigues Brandão de Paiva, Maria Carolina Andrade Guerra, Daniel Vitor Vasconcelos-Santos, Sílvia Ligório Fialho, Lorena Carla Vieira |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Immunology Anti-Inflammatory Agents Inflammation Retina Autoimmune Diseases Pathogenesis Uveitis 03 medical and health sciences 0302 clinical medicine Antigen Panuveitis medicine Immunology and Allergy Animals Humans Peroxidase Pharmacology biology business.industry medicine.disease Mycobacterium bovis Thalidomide 030104 developmental biology 030220 oncology & carcinogenesis Myeloperoxidase Intravitreal Injections Models Animal biology.protein Histopathology Rabbits medicine.symptom business medicine.drug |
| Zdroj: | International immunopharmacology. 81 |
| ISSN: | 1878-1705 |
| Popis: | Uveitis encompasses a heterogeneous and complex group of conditions characterized by intraocular inflammation, frequently affecting young individuals and representing an important cause of irreversible blindness worldwide. Animal models have been critical to understand etiology and pathogenesis of uveitis, being also employed to assess new therapeutic strategies, preceding human studies. However, there is still a need of developing and studying different models, due to the difficulties in recapitulating all forms of human uveitis effectively. Although corticosteroids are usually the first-line therapy for non-infectious uveitis, their long-term use is limited by potentially serious side effects in all possible delivery routes. Thus, thalidomide, a drug with anti-inflammatory and antiangiogenic properties, was investigated in a novel experimental model of uveitis, induced by Mycobacterium bovis Calmette-Guerin Bacillus (BCG), in rabbits. The experimental protocol consisted of two subcutaneous injections of BCG, followed by two intravitreal injections of the same antigen, inducing panuveitis. Animals were treated with a single intravitreal injection of thalidomide suspension or PBS. Clinical manifestations of uveitis improved after intravitreal thalidomide, involving both anterior and posterior segments. Protein content, N-acetyl-b-glucosaminidase (NAG) and myeloperoxidase (MPO) activities were elevated in ocular tissues after disease induction, further decreasing post-treatment with intravitreal thalidomide. This therapeutic response was also confirmed on ocular electrophysiology, as well as histopathology. This experimental model induced panuveitis in rabbits using a low-cost mycobacterial antigen, with intraocular inflammation subsequently improving after treatment. Intravitreal thalidomide may be a potential alternative to treat intraocular inflammation in corticosteroid-sparing therapies. |
| Databáze: | OpenAIRE |
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