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The effect of human posterior corneal stromal cells on corneal endothelial cell maintenance

Wongvisavavit, Rintra; (2023) The effect of human posterior corneal stromal cells on corneal endothelial cell maintenance. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Corneal transparency depends on the function of corneal endothelial cells (CECs). As CECs rarely proliferate in vivo and the number of cells declines with age, hence any damage to or dysfunction of CECs could lead to corneal blindness. Since, posterior corneal stromal cells lie in close anatomical proximity to CEC, it was hypothesised that they might play a role in CEC proliferation inhibition. For the first time, corneal stromal cells isolated from the posterior stromal layer of normal human donor corneas. The cells were cultured and differentiated into keratocytes expressing their requisite markers (keratocan, lumican and ALDH3A1). After embedding the keratocytes in Real Architecture For 3D Tissue (RAFT), they retained their characteristics. Posterior corneal keratocytes were co-cultured with human corneal endothelial cell line (HCECL) using an inverted indirect co-cultured model. CEC proliferation was found to be elevated in this situation. Epithelial-derived neutrophil-activating peptide 78 (ENA-78 or CXCL5), was found to be secreted from posterior corneal keratocytes, promoted CEC proliferation via binding to CXCR2 (G-coupled protein receptor) and the signal was transduced through the extracellular signal regulated kinase1/2 (ERK1/2) mediated signaling pathway. Moreover, CEC wound healing was promoted after treating the cells with 20 ng/mL of ENA-78. In addition, HCECLs expressed the CEC markers, zonula occludens-1 (ZO-1) and Na⁺/K⁺-ATPase after being cultured in ENA-78. Likewise, CEC wound healing study using primary human corneal endothelial cells (p-HCEC), obtained from donor corneas, showed similar results. In the ex vivo study, ENA-78 promoted CEC wound closure with a cell migration morphology observed at the wounded edge after alizarin red staining. This study highlights the possibility of using ENA-78 as a medicinal treatment as an alternative to corneal transplantation.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The effect of human posterior corneal stromal cells on corneal endothelial cell maintenance
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10168924
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