Intravitreal thalidomide ameliorates inflammation in a model of experimental uveitis induced by BCG

Autor(es)

Moreira Castro, Brenda Fernanda ^[1] ; Vieira, Lorena Carla ^[1] ; Vasconcelos-Santos, Daniel Vitor ^[2] ; de Freitas Cenachi, Sarah Pereira ^[2] ; Lacerda Cotta, Oliver Araujo ^[3] ; Andrade Guerra, Maria Carolina ^[3] ; Brandao Paiva, Mayara Rodrigues ^[1] ; Silva, Luciana Maria ^[4] ; Silva-Cunha, Armando ^[1] ; Fialho, Silvia Ligorio ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Fac Pharm, 6627 Presidente Antonio Carlos Ave, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Fed Minas Gerais, Fac Med, 190 Prof Alfredo Balena Ave, BR-30130100 Belo Horizonte, MG - Brazil

^[3] Ezequiel Dias Fdn, Pharmaceut Res & Dev, 80 Conde Pereira Carneiro St, BR-30510010 Belo Horizonte, MG - Brazil

^[4] Ezequiel Dias Fdn, Cell Biol Lab, 80 Conde Pereira Carneiro St, BR-30510010 Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 81, APR 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático