Project: A05

The role of limbal mesenchymal stem cells in corneal (lymph)angiogenesis, inflammation and UV-induced pterygium pathogenesis

The ocular limbus is the junction between the avascular cornea and the heavily (lymph)vascularized conjunctiva. It is also the habitat of limbal epithelial stem cells (LESC) which maintain the integrity of corneal epithelium, the outermost layer of the cornea.The limbal barrier for neovascularization and inflammation may be compromised leading to reduced vision. This occurs e.g. in pterygium, a UV-induced fibro-vascular tumour affecting 12% of people worldwide, which advances onto the cornea surface causing immune cell infiltration, neovascularization and, if left untreated, blindness.

The pterygium stroma contains cells, which contribute to the characteristic hyperplasia and fibrosis via myofibroblast hyperproliferation and cross talk with the epithelium. UV also induces DNA damage that has consequences ranging from cell fate alterations such as senescence and stem cell depletion to inflammatory and metabolic responses. We previously showed that LESC, playing a pivotal role in corneal avascularity, become differentiated under UV exposure, while producing pro-inflammatory cytokines. We also found that UV irradiation of LESCs and limbal fibroblasts leads to differentiation characterized by SC marker loss, an upregulation of proinflammatory factors and fibrosis-related proteins.

In this project, we will investigate a novel limbal mesenchymal stem cell (LMSC) population which has therapeutic potential but on the other hand, when UV damaged, is involved in pterygium pathogenesis.

The elucidation of the potential immunoregulatory properties as well as the UV-induced (lymph)angiogenic and inflammatory effects employed by LMSC will contribute to the development of new therapeutic strategies against corneal neovascularization/inflammation and pterygium progression and recurrence.

Key methods: primary cell culture, cell culture assays, flow cytometry, cell sorting, proteomics, image analysis, transgenic mouse models, RNASeq, bioinformatics, shRNA, IHC, IF