The role of ABCB5-expressing limbal epithelial stem cells in corneal lymphangiogenic privilege and pterygium pathogenesis

• Applicant: Maria Notara, Ph.D.
• Subject Area: Ophthalmology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257498687

Limbal epithelial stem cells (LESC) are localized at the junction between the avascular cornea and the heavily (lymph)vascularized conjunctiva. LESC maintain the integrity of the corneal epithelium and express ABCB5, which is a limbal stem cell gene required for corneal development and repair. Although it has been proven both clinically and experimentally that LESC destruction compromises corneal avascularity, the exact mechanisms behind this remain unclear.Exposure to UV irradiation is one mechanism known to compromise the LESC niche and is associated with pterygium, a non-cancerous tumour of the conjunctiva which grows onto the cornea and compromises corneal avascularity and vision. Our own preliminary data suggest that limbal epithelial stem cells become differentiated under UV exposure, thus leading to a pro-inflammatory and prolymphangiogenic micromillieu in the limbal stem cell niche. Furthermore, our own early data show damage to ABCB5+ LESC in human pterygium tissue. Our overall hypothesis is that while under normal circumstances, LESCs expressing ABCB5 contribute to corneal avascularity, following UV-induced damage they contribute to neovascularization and induction of pterygia.Therefore, we aim to: 1. better understand the molecular mechanisms by which ABCB5-positive LESCs contribute to corneal avascularity and thereby identify novel regulators of corneal lymphangiogenic privilege and 2. unravel if and how UV light, known to be associated with pterygium pathogenesis, damages ABCB5-positive LESCs. Overall, a better understanding of the putative anti(lymph)angiogenic mechanisms exerted by ABCB5-positive limbal epithelial stem cells and their potential damage by UV light will eventually help to develop new treatment options against neovascular corneal and ocular surface diseases.

• DFG Programme: Research Units
• Subproject of: FOR 2240: (Lymph)Angiogenesis And Cellular Immunity In Inflammatory Diseases Of The Eye
• Co-Investigators: Professor Dr. Claus Cursiefen; Professor Dr. Björn Schumacher