Associated Principal Investigator, Department of Ophthalmology
Dr. Maria Notara
Associate Principal Investigator
Building: LFI Gebäude 13
Kerpener Straße 62
Vision is a key sensory function. Clear vision depends on transparency of the structures of the visual axis. Consequently, normal corneal tissue (the “windscreen of the eye”) is in an avascular and low inflammatory state.
The limbal epithelial stem cells (LESC) maintain the integrity of the corneal epithelium, preventing neovascularization, stromal scarring, and conjunctivalization. Although it has been proven both clinically and experimentally that LESCs destruction compromises corneal avascularity, the exact mechanisms by which this is achieved remain unidentified.
Our research: Our group focuses on elucidating these mechanisms and aims to identify new LESC-related regulators of corneal neovascularisation, which will lead to new therapeutic options (we are part of FOR2240, “(Lymph)angiogenesis and cellular immunity in inflammatory diseases of the eye”).
Exposure to UV irradiation compromises the LESC niche and induces corneal (lymph)angiogenesis. Pterygium, a non-cancerous tumour of the conjunctiva, is linked to UV-induced DNA and oxidative damage. The phenotype is associated with inflammation and neovascularisation causing discomfort and decrease of vision.
Preliminary evidence links pterygium onset to limbal epithelial stem cell (LESC) deficiency and own data suggest that following short-term UV irradiation LESC become differentiated. However, a direct involvement of LESC DNA damage in the disease is not fully explored.
Our hypothesis is that after UV-induced damage the inability of LESCs to repair DNA damage contributes to induction of pterygia. In collaboration with the laboratory of Professor Björn Schumacher we will aim to investigate the possible links between UV damage and neovascularization using a nucleotide excision repair-deficient mouse model. We will investigate the association of ERCC1 with pterygium and the possibility of using the ERCC deficient mouse as a model for UV-induced alterations relevant to pterygium.
Also, we will explore the role of photolyase, a DNA repairing enzyme, as a therapeutic approach to prevent UV induced LESC damage leading to neovascularization, inflammation and thus pterygium.
Our goals: Pterygium has a higher prevalence in countries with elevated ultraviolet exposure. It is estimated that an expected 10% of all refugees who came to Germany from southern countries will most likely suffer from pterygium (i.e.>100000), resulting in a significant burden to the health system. Therefore, we aim to elucidate the mechanisms underlying the disease and thus help towards developing more efficient prevention and treatment strategies.
Figure 1: A. Location of the limbus, the barrier between physiologically hem- and lymph-vascularized conjunctiva and avascular and transparent cornea. Limbal stem cells are located in the limbal region of the eye, along the dashed line. B. The arrows highlight the vascular plexus which is visible in the conjunctiva and stops at the limbus.
Figure 2: The limbal epithelial stem cells (normally residing in the basal layers of the limbus) give rise to transient amplifying cells which migrate towards the superficial layers of the corneal area and ultimately form the terminally differentiated epithelium.
Figure 3: Schematic representation of the peripheral light focusing effect, occurring on the nasal limbus. This site is associated with increased incidence of pinguecula and pterygium, conjunctival tumors which are associated with UV damage.
Figure 4: Schematic representation of the effects of Ultraviolet B irradiation on the limbal niche. UVB irradiation affects limbal epithelial cells by reducing their putative stem cell phenotype as well as increasing their proinflammatory paracrine action. While UVB irradiated limbal fibroblasts reduce their pro-lymphangiogenic effect, they lose their ability to maintain the limbal epithelial stem cell character and they also contribute to inflammation. As a result, the niche function is disrupted and the increased proinflammatory milieu causes the infiltration of immune cells such as macrophages and neutrophils, leading to pathologic hem- and lymphangiogenesis.