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Title
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Roadblocks on the tissue-engineering path towards conjunctival restoration : the hidden truth behind the in vitro functionality of cultured goblet cells and the ancient pterygium pathology
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Author
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Abstract
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| Many consider the cornea the window of the eye, making the neighboring conjunctiva to be often overlooked. However, correct conjunctival functioning is indispensable for the maintenance of ocular surface homeostasis and, consequently, for creating an optimal environment for corneal epithelial cell renewal. It is therefore not surprising that a wide range of ocular surface pathologies are characterized by conjunctival damage or compromised performances. Standard practice of care includes the surgical removal of the affected conjunctiva and covering the open 'wound' to avoid structural alterations and permanent scar formation related to secondary healing. The most optimal conjunctival substitute for this 'wound' coverage is yet to be defined. The emerging field of tissue engineering in ophthalmology offers the possibility to address the limitations of the current conjunctival substitutes, opening new horizons in treatment options for those with severe cicatrizing conjunctivitis as well as other pathologies such as pterygium, bleb leaks following trabeculectomy, and extensive nevi. The end-point of this development road would be an appropriate tissue-engineered graft, potentially adaptable to a specific disease location, damage type, or patient population. However, considerable roadblocks are to be addressed before conjunctival tissue engineering can be implemented as a treatment option. In this PhD thesis, two different types of roadblocks were investigated. The first obstacle relates to a proper cell characterization of the cultured conjunctival epithelium, which is currently lacking. Ex vivo expanded conjunctival cultures were established in a serum-free environment using an explant culture technique. To ensure short- and long-term rehabilitation, the cultured epithelium should consist of barrier-forming squamous epithelial cells, gel-forming mucin secreting goblet cells, and self-renewing stem cells. A marker panel for the immunocytochemical identification of these three cultured conjunctival cell types has been drafted. However, the contradicting results obtained with the state-of-the-art markers for conjunctival goblet cells led us to re-evaluate their characterization as well as their ex vivo functionality. The second hurdle corresponds to the path that is undeniably intertwined with the development of a tissue-engineered graft and could be summarized as the unwavering need to understand the underlying pathology as novel approaches are drafted. During this thesis, patients suffering from pterygium have been taken as a patient group that would significantly benefit from a conjunctival reconstruction. To further improve the treatment strategy, questions surrounding its origin, pathophysiology, and recurrence have therefore been addressed. |
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Language
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English
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Publication
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Antwerp
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University of Antwerp, Faculty of Medicine and Health Sciences, Department of Translational Neurosciences
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2022
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Volume/pages
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216 p.
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Note
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Koppen, Carina [Supervisor]
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Zakaria, Nadia [Supervisor]
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Pintelon, Isabel [Supervisor]
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Full text (open access)
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