Symposien Freitag

Stern and coworkers coined the term “lacrimal functional unit” or LFU. Due to them the LFU comprises the lacrimal glands (both main and accessory), the ocular surface and the interconnecting innervation. In the course of the last decade the definition of LFU has been broadened as further components of the ocular surface and lacrimal apparatus came into focus, such as the meibomian glands, the lid wiper or distinct tear film components. The talk will briefly summarize the current knowledge about the LFU and present promising and ongoing research topics. Surfactant proteins (SP) assist the formation of a monolayer of surface- active phospholipids at the liquid-air interface of the alveolar lining, play a major role in lowering surface tension of interfaces, and have functions in immune defense. Recently, a putative new SP (SFTA3 or SP-H) was identified. By means of computational chemistry and molecular-biology we have localized and characterized SP-H. SP-H expression was analyzed in tissues of the ocular surface and in tear fluid. The regulation of SP-H transcription was studied in ocular surface cell lines after incubation with ocular pathogens. The protein concentration of SP-H was measured by ELISA in tears from patients suffering from dry eye disease (DED). The localization of SP-H in ocular surface tissues, sequence based prediction tools for posttranslational modifications and molecular dynamic simulations revealed that SP-H has physicochemical properties similar to the already known SPs B and C. Stimulation experiments in cell lines with pathogens showed an increased expression of SP-H. In tears from DES patients SP-H concentration was increased. The results indicate SP-H as a new SP of the tear film which represents an until now unknown SP class. SP-H is regulated under experimental inflammatory conditions and in cases of DED.

The application of lacrimal gland-derived mesenchymal stem cells (LG-MSC) for the regeneration of lacrimal gland tissue could result in a novel therapy in dry eye syndrome. Purpose of this study was to evaluate the influence of low oxygen on the phenotype, the differentiation potential and the proliferative and regenerative capacity of murine LG-MSC. Compared to 21% oxygen, in 5% oxygen LG-MSC showed a stable morphology, higher colony forming potential and an increased proliferation capacity. Furthermore culture medium from MSC expanded in 5% oxygen significantly enhanced migration and proliferation in lacrimal gland epithelial cells.

Transcription factors play important roles in differentiation programs and have been used as tools to direct progenitor cells towards specific lineages. This contribution discusses transcriptional regulators potentially involved in regeneration and differentiation of corneal epithelial cells. A focus is placed on members of the SOX (Sry-related HMG box) gene family, which are preferentially expressed in adult human limbal epithelial cells.

Ultraviolet light B (UVB)-irradiation is linked to ocular pathologies such as pterygium. Despite the large indirect evidence connecting UVB irradiation to limbal epithelial stem cell (SC) damage, their precise reactions to UVB irradiation are unclear. Our group focuses on the responses of the cellular components of the limbal niche to UVB including effects on putative stem cell phenotype, the ability of accessory niche cells to support SC and changes in the pro-inflammatory and (lymph)angiogenic milieu.

Limbal stem cell deficiency (LSCD) is an eye disorder where the stem cells responsible for forming the surface skin of the cornea are destroyed by disease. This results in pain, loss of vision and a cosmetically unpleasant appearance. Many new treatments, including stem cell therapies, are emerging for the treatment of this condition but assessment of these new technologies is severely hampered by the lack of biomarkers for this disease or validated tools for assessing its severity. The aims of this study were use validated and objective outcome measures to evaluate the three-year outcomes for allogeneic ex-vivo cultivated limbal epithelial transplantation (allo-CLET) in patients who had bilateral total LSCD secondary to aniridia or Stevens Johnson syndrome (SJS). The results demonstrate that following allo-CLET there was a decrease in LSCD severity and an increase in visual acuity which persisted for 12 months following treatment. Once immunosuppression was stopped at 12 months post transplantation, the signs of LSCD recurred and visual acuity deteriorated. At 3 years post treatment only 30% of patients showed a prolonged benefit from treatment.