Document Type
Journal Article
Publication Title
Cells
Volume
12
Issue
13
PubMed ID
37443766
Publisher
MDPI
School
School of Medical and Health Sciences
RAS ID
61839
Funders
https://doi.org/10.3390/cells12131731
Abstract
The limbus, the vascularized junction between the cornea and conjunctiva, is thought to function as a barrier against corneal neovascularization. However, the exact mechanisms regulating this remain unknown. In this study, the limbal epithelial stem cell (LESC) marker ABCB5 was used to investigate the role of LESCs in corneal neovascularization. In an ABCB5KO model, a mild but significant increase of limbal lymphatic and blood vascular network complexity was observed in developing mice (4 weeks) but not in adult mice. Conversely, when using a cornea suture model, the WT animals exhibited a mild but significant increase in the number of lymphatic vessel sprouts compared to the ABCB5KO, suggesting a contextual anti-lymphangiogenic effect of ABCB5 on the limbal vasculature during development, but a pro-lymphangiogenic effect under inflammatory challenge in adulthood. In addition, conditioned media from ABCB5-positive cultured human limbal epithelial cells (ABCB5+) stimulated human blood and lymphatic endothelial cell proliferation and migration. Finally, a proteomic analysis demonstrated ABCB5+ cells have a pro(lymph)angiogenic as well as an anti-inflammatory profile. These data suggest a novel dual, context-dependent role of ABCB5+ LESCs, inhibiting developmental but promoting inflammatory (lymph)angiogenesis in adulthood and exerting anti-inflammatory effects. These findings are of high clinical relevance in relation to LESC therapy against blindness.
DOI
10.3390/cells12131731
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Meshko, B, Volatier, T. L. A., Hadrian, K., Deng, S., Hou, Y., Kluth, M. A., . . . Notara, M. (2023). ABCB5+ limbal epithelial stem cells inhibit developmental but promote inflammatory (lymph) angiogenesis while preventing corneal inflammation. Cells, 12(13), article 1731. https://doi.org/10.3390/cells12131731