Gabriella M Fernandes-Cunha1,2,3,4, Silvia Ligório Fialho5, Gisele Rodrigues da Silva6,7,8,9, Armando Silva-Cunha10, Min Zhao6,7,8, Francine Behar-Cohen6,7,8. 1. Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. gabriellafcunha@gmail.com. 2. INSERM UMRS 1138, Team 17, Centre de Recherche des Cordeliers, 75006, Paris, France. gabriellafcunha@gmail.com. 3. Pierre and Marie Curie University, 75005, Paris, France. gabriellafcunha@gmail.com. 4. Paris Descartes University, 75006, Paris, France. gabriellafcunha@gmail.com. 5. Pharmaceutical and Biotechnological Development, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil. 6. INSERM UMRS 1138, Team 17, Centre de Recherche des Cordeliers, 75006, Paris, France. 7. Pierre and Marie Curie University, 75005, Paris, France. 8. Paris Descartes University, 75006, Paris, France. 9. Faculty of Pharmacy, Federal University of São João Del Rei, Divinópolis, Minas Gerais, Brazil. 10. Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Abstract
BACKGROUND: Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels. METHODS: Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR. RESULTS: After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1β, TNF-α, IL-6), VEGF, and iNOS at day 30. CONCLUSION: These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis.
BACKGROUND:Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels. METHODS: Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR. RESULTS: After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1β, TNF-α, IL-6), VEGF, and iNOS at day 30. CONCLUSION: These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis.
Authors: Gabriella M Fernandes-Cunha; Cíntia M F Rezende; Wagner N Mussel; Gisele R da Silva; Elionai C de L Gomes; Maria I Yoshida; Sílvia L Fialho; Alfredo M Goes; Dawison A Gomes; Ricardo W de Almeida Vitor; Armando Silva-Cunha Journal: J Mater Sci Mater Med Date: 2015-12-16 Impact factor: 3.896
Authors: William J Brock; Christopher J Somps; Vince Torti; James A Render; Jeffrey Jamison; Maria I Rivera Journal: Int J Toxicol Date: 2013-04-24 Impact factor: 2.032
Authors: Stefanie Ebert; Tobias Schoeberl; Yana Walczak; Katharina Stoecker; Thomas Stempfl; Christoph Moehle; Bernhard H F Weber; Thomas Langmann Journal: J Leukoc Biol Date: 2008-06-12 Impact factor: 4.962
Authors: Rodrigo Jorge; Igor Neves Coelho; Armando Silva-Cunha; Gabriella Maria Fernandes Cunha; Ingrid U Scott; Silvia Ligório Fialho; João Marcello Furtado Journal: Am J Ophthalmol Case Rep Date: 2021-04-16