Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach
Polypoidal choroidal vasculopathy (PCV), an Asian-predisposed ocular disease subtype, is characterized by haemorrhagic and polyp-like dilatations of blood vessels in the choroid. Using human blood outgrowth endothelial cells (BOECs) for disease modelling, we performed RNA-sequencing on PCV and norma...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
| Published: |
Nanyang Technological University
2022
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/155373 |
| _version_ | 1826126921583296512 |
|---|---|
| author | Yeo, Natalie Jia Ying |
| author2 | Christine Cheung |
| author_facet | Christine Cheung Yeo, Natalie Jia Ying |
| author_sort | Yeo, Natalie Jia Ying |
| collection | NTU |
| description | Polypoidal choroidal vasculopathy (PCV), an Asian-predisposed ocular disease subtype, is characterized by haemorrhagic and polyp-like dilatations of blood vessels in the choroid. Using human blood outgrowth endothelial cells (BOECs) for disease modelling, we performed RNA-sequencing on PCV and normal BOECs in response to heterogeneous flow as a disease-relevant stressor. Functionally, PCV BOECs displayed repressed mitochondrial function and abnormal superoxide increases under heterogeneous flow stress. Notably, transcriptomic analyses revealed intrinsic endothelial perturbations of cell adhesion and extracellular matrix (ECM) organization in PCV, as well as downregulated CLDN5 that is a tight junction component. Functionally, baseline PCV BOECs exhibited lower transendothelial electrical resistance, suggesting decreased barrier integrity. In conclusion, ECM regulation and barrier dysfunction may underlie PCV polyp formation with altered mitochondrial flow responses exacerbating endothelial dysfunction upon turbulent flow. This thesis describes a novel endothelial cellular model for PCV and highlights endothelial phenotypes amenable to therapeutic restoration. |
| first_indexed | 2024-10-01T07:00:18Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/155373 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:00:18Z |
| publishDate | 2022 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1553732023-03-05T17:10:00Z Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach Yeo, Natalie Jia Ying Christine Cheung Lee Kong Chian School of Medicine (LKCMedicine) ccheung@ntu.edu.sg Science::Biological sciences Polypoidal choroidal vasculopathy (PCV), an Asian-predisposed ocular disease subtype, is characterized by haemorrhagic and polyp-like dilatations of blood vessels in the choroid. Using human blood outgrowth endothelial cells (BOECs) for disease modelling, we performed RNA-sequencing on PCV and normal BOECs in response to heterogeneous flow as a disease-relevant stressor. Functionally, PCV BOECs displayed repressed mitochondrial function and abnormal superoxide increases under heterogeneous flow stress. Notably, transcriptomic analyses revealed intrinsic endothelial perturbations of cell adhesion and extracellular matrix (ECM) organization in PCV, as well as downregulated CLDN5 that is a tight junction component. Functionally, baseline PCV BOECs exhibited lower transendothelial electrical resistance, suggesting decreased barrier integrity. In conclusion, ECM regulation and barrier dysfunction may underlie PCV polyp formation with altered mitochondrial flow responses exacerbating endothelial dysfunction upon turbulent flow. This thesis describes a novel endothelial cellular model for PCV and highlights endothelial phenotypes amenable to therapeutic restoration. Doctor of Philosophy 2022-02-18T05:01:38Z 2022-02-18T05:01:38Z 2022 Thesis-Doctor of Philosophy Yeo, N. J. Y. (2022). Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/155373 https://hdl.handle.net/10356/155373 10.32657/10356/155373 en MOE2018-T2-1-042 SPF2014/002 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Science::Biological sciences Yeo, Natalie Jia Ying Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach |
| title | Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach |
| title_full | Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach |
| title_fullStr | Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach |
| title_full_unstemmed | Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach |
| title_short | Elucidating endothelial pathology in polypoidal choroidal vasculopathy : a patient-derived cellular model approach |
| title_sort | elucidating endothelial pathology in polypoidal choroidal vasculopathy a patient derived cellular model approach |
| topic | Science::Biological sciences |
| url | https://hdl.handle.net/10356/155373 |
| work_keys_str_mv | AT yeonataliejiaying elucidatingendothelialpathologyinpolypoidalchoroidalvasculopathyapatientderivedcellularmodelapproach |