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The effect of UVA-induced limbal epithelial stem cell DNA damage and implications in corneal inflammation and neovascularisation

Subject Area Ophthalmology
Term since 2025
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 568930210
 
The cornea is our window to the world. The outermost layer, the epithelium is maintained by a population of stem cells which inhabit the space between the normally avascular cornea and the heavily (lymph)vascularized conjunctiva while expressing the marker ABCB5. Chronic exposure to solar UV irradiation is a known threat to the stem cell niche and is linked to the pathogenesis of pterygium, a benign tumor thought which can affect vision. While previously photo-ageing and carcinogenesis studies were focusing on the high-energy UVB, more recent own and other group reports suggest a decisive role of UVA which penetrates deeper in tissues causing extensive damage. Specifically, we have shown that the stem cells lose their characteristics following both UVA and UVB exposure, thus leading to undesired inflammatory and pro-angiogenic conditions. Our study hypothesis is that chronic UVA exposure via sunlight affects ABCB5-expressing stem cells and contributes to corneal vascularization and initiation of pterygia. To test this hypothesis we will try to understand the mechanisms by which UVA-damaged ABCB5-positive stem cells contribute to corneal neovascularization and inflammation as well as to investigate the role of UVA-induced DNA damage known to pterygium pathogenesis and whether DNA-repairing pharmaceutical intervention may improve disease outcome. On the whole, an improved understanding of the anti-angiogenic mechanisms exerted by ABCB5-positive stem cells and their potential damage by UVA light will help to develop new treatment options against neovascular corneal and ocular surface diseases.
DFG Programme Research Grants
International Connection Netherlands
 
 

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