2018-05-162018-03-27SILVA, A. C. G. Desenvolvimento de modelo biomimético de córnea para avaliação da toxicidade ocular de produtos farmacêuticos: perfil inflamatório, caracterização e aplicabilidade. 2018. 111 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2018.http://repositorio.bc.ufg.br/tede/handle/tede/8480Introduction: Cosmetic products eye toxicity assessment has been performed worldwide using alternative methods since animal testing has been banished for this purpose in many countries. In this context, reconstructed epithelial models have been used internationally for these evaluations, which are not available in Brazil due bureaucratic issues that limit their acquisition and use in national territory. Objective: In this work, an evaluation platform based on cellular inflammatory changes caused by exposure to eye irritants was proposed, as well as the development of a biomimetic corneal model from human keratinocytes, which was characterized and evaluated for applicability in ocular toxicity studies. Methods: Inflammatory profile of HaCat keratinocytes was determined after exposure to 13 different chemicals with different classification for ocular irritation (irritants and non-irritants) using Cytometric Bead Array (CBA) and ELISA methods. 3D models were obtained by cultivating HaCat cell line onto a collagen type I matrix, in air-liquid interface for five days. Morphological characterization was carried out through Hematoxylin-eosin staining and corneal epithelial biomarkers expression was assessed using indirect immunofluorescence. Predictive capacity assessment was performed by exposure of model to test substances with subsequently tissue viability assessment. Finally, applicability of system was verified by testing five marketed eyebrow Henna samples which were considered non-irritants due the lack of adequate labelling. Results and Discussion: A qualitative and quantitative correlation was established regarding the HaCat cells inflammatory profile and eye irritation degree of evaluated substances. The epithelial model presented similar morphology and biomarkers expression patterns similar to the found in human corneal epithelium, so that tissue viability after exposure to test substances reduced proportionately to the irritant potential of them. Furthermore, 3D model classified four of the five evaluated Henna samples as moderate or mild irritants. Conclusion: The developed epithelial model presented morphological and functional properties similar to those founded in human corneal epithelium, which enabled the distinction between irritants and non-irritants and it is also applicable to the investigation of botanical mixtures ocular toxicity potential.application/pdfAcesso AbertoCaracterização morfofuncionalModelo biomimético de córneaPerfil inflamatórioToxicidade ocularMorphofunctionalCharacterizationBiomimetic corneal modelInflammatory profileOcular toxicityCIENCIAS BIOLOGICAS::FARMACOLOGIADissertação