Chapitre 1 Matrix metalloproteinases and their inhibitors in Fuchs endothelial corneal dystrophy
2.4 Perspectives de recherche
De plus amples expériences sont nécessaires afin de valider le rôle des MMPs dans la DECF. D’ailleurs, une suite à ce projet est déjà prévue. Par exemple, étant donné la baisse importante de MMP-10 observée chez les CECs DECF, nous aimerions
établir si une modulation (inhibition/activation) de la MMP-10 chez l’endothélium cornéen de patients sains et DECF mène à une modification de la MEC (accumulation/diminution). Pour ce faire, nous prévoyons de mettre en culture des CECs DECF et saines sur des lamelles de verre et les incuber avec de la MMP-10 ou TIMPs. Nous voulons par la suite évaluer le dépôt de MEC par IF en détectant la fibronectine, la laminine et le collagène de type IV (les principales composantes des guttae) dans le but d’évaluer l’effet de la MMP-10 et de son inhibition sur la MEC déposée. Nous avons d’ailleurs déjà testé la faisabilité de cette expérience en faisant déposer de la MEC par des CECs DECF et saines. Les CECs commencent à déposer de la MEC dès la première semaine post-confluence. De plus, nous avons observé que les CECs DECF semblent déposer plus de MEC que les CECs saines, confirmant que les CECs DECF conservent leur comportement pathologique in vitro.
Conclusion
Ce projet a mené à de nouvelles découvertes concernant les MMPs dans la DECF. Nous avons observé des différences intéressantes entre le profil des MMPs provenant de CECs DECF et celui provenant des CECs saines, autant au niveau de CECs in vitro que de spécimens natifs ex vivo. De plus, nous avons mis de l’avant l’influence de la morphologie cellulaire sur le profil des MMPs et des TIMPs et plus spécifiquement le fait que les CECs DECF ne sont pas influencées de la même façon que les CECs saines. Nos travaux suggèrent donc une contribution possible des MMPs dans la physiopathologie de la DECF, plus précisément, une contribution dans le processus d’accumulation excessive de MEC dans la DECF.
L’identification éventuelle d’une protéase clé pourrait mener au développement de nouvelles voies thérapeutiques, visant par exemple la dégradation des excroissances de la membrane basale vues dans la DECF, ce qui éviterait le recours aux greffes pour le traitement de cette maladie. En effet, l’utilisation de protéase telle la MMP-3 a déjà été suggérée comme traitement potentiel d’une maladie oculaire partageant un problème de MEC semblable à la DECF [201]. Les résultats de ce projet représentent donc un début qui pourrait aboutir à de réels changements dans les traitements disponibles et donc la vie des patients DECF.
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