Maria Notara

Department of Ophthalmology

Cornea Stem Cell Biology Group

The aim of this research group is to understand the mechanisms underlying the role of the limbal stem cells in corneal avascularity. Specifically, we are interested in the effect of UV irradiation on the limbal stem cell phenotype and pathological neovascularisation.

Research Focus

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 thus preventing neovascularization, stromal scarring and conjunctivalisation (Figure 1.). These stem cells express the ATP binding cassette subfamily B member 5 (ABCB5), an ABC transporter and P-glycoprotein family member principally expressed in normal as well as cancerous stem cell populations. Although it has been proven both clinically and experimentally that LESC destruction compromises corneal avascularity, the exact mechanisms by which this is achieved remain unidentified.

Our group focuses on elucidating these mechanisms and aims to identify new LESC-related regulators of corneal neovascularisation which will lead to new therapeutic approaches.

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. 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.

Preliminary evidence links pterygium onset to limbal epithelial stem cell (LESC) deficiency and our own data suggest that following short term UV irradiation LESCs become differentiated. However, a direct involvement of LESC DNA damage in the disease is not fully explored.

Our Goals

Our hypothesis is that following UV insult, the inability of these stem cell populations to repair DNA damage (Figure 2) contributes to induction of pterygia. In collaboration with the laboratory of Professor Björn Schumacher (CECAD) we investigate the possible links between stem cell UV damage and neovascularization. Among other projects, we explore the utilization of photolyase, a DNA repairing enzyme, as a therapeutic approach to prevent UV induced LESC damage leading to neovascularization, inflammation and thus pterygium. So far, we have demonstrated that exogenous or transgenically expressed DNA repairing enzymes show great promise in the treatment of CPD lesions, but the complete clearance of CPDs from the limbal stem cell zone remains a challenge. (Volatier et al., Biology, 2022).

In addition, we are studying ABCB5-expressing limbal epithelial and mesenchymal stem cell populations in the human limbus which we have shown to be involved in the pterygium progression and its associated fibrosis. Specifically, we discovered a novel dual, context-dependent role of ABCB5+ LESCs, inhibiting developmental but promoting inflammatory (lymph)angiogenesis in adulthood and exerting anti-inflammatory effects (Figure 3). These findings are of high clinical relevance in relation to LESC therapy against blindness. (Meshko et al., Cells, 2023).

We are part of FOR2240, “(Lymph)angiogenesis and cellular immunity in inflammatory diseases of the eye”) and the new CRC 1607 ‘Immunomodulating and anti(lymph)angiogenic therapies for age-related eye diseases that can lead to blindness’.

Key Publications

  1. Meshko, B., et al… and Notara, M, ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation. Cells, 2023.
  2. Volatier, T., et al… and Notara, M, Short-Term UVB Irradiation Leads to Persistent DNA Damage in Limbal Epithelial Stem Cells, Partially Reversed by DNA Repairing Enzymes. Biology (Basel), 2023.
  3. Volatier, T., et al… and Notara, M, UV Protection in the Cornea: Failure and Rescue. Biology (Basel), 2022.
  4. Domdey, M., et al… and Notara, M, Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium. Stem Cell Res, 2022.
  5. Notara, M., et al., UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation. Sci Rep, 2018.