Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression

New laser design for NIR lidar applications

Recently, we quantified the very high spatio-temporal short term variability of tropospheric water vapor in a three dimensional study [1]. From a technical point of view this also depicted the general requirement of short integration times for recording water-vapor profiles with lidar. For this purpose, the only suitable technique is the differential absorption lidar (DIAL) working in the near-infrared (NIR) spectral region. The laser emission of most water vapor DIAL systems is generated by Ti:sapphire or alexandrite lasers. The water vapor absorption band at 817 nm is predominated for the use of Ti:sapphire. We present a new concept of transversely pumping in a Ti:Sapphire amplification stage as well as a compact laser design for the generation of single mode NIR pulses with two different DIAL wavelengths inside a single resonator. This laser concept allows for high output power due to repetitions rates up to 100Hz or even more. It is, because of its compactness, also suitable for mobile applications

New laser design for NIR lidar applications

Recently, we quantified the very high spatio-temporal short term variability of tropospheric water vapor in a three dimensional study [1]. From a technical point of view this also depicted the general requirement of short integration times for recording water-vapor profiles with lidar. For this purpose, the only suitable technique is the differential absorption lidar (DIAL) working in the near-infrared (NIR) spectral region. The laser emission of most water vapor DIAL systems is generated by Ti:sapphire or alexandrite lasers. The water vapor absorption band at 817 nm is predominated for the use of Ti:sapphire. We present a new concept of transversely pumping in a Ti:Sapphire amplification stage as well as a compact laser design for the generation of single mode NIR pulses with two different DIAL wavelengths inside a single resonator. This laser concept allows for high output power due to repetitions rates up to 100Hz or even more. It is, because of its compactness, also suitable for mobile applications

Tumorcode

During the past years our group published several articles using computer simulations to address the complex interaction of tumors and the vasculature as underlying transport network. Advances in imaging and lab techniques pushed in vitro research of tumor spheroids forward and animal models as well as clinical studies provided more insights to single processes taking part in tumor growth, however, an overall picture is still missing. Computer simulations are a non-invasive option to cumulate current knowledge and form a quasi in vivo system. In our software, several known models were assembled into a multi-scale approach which allows to study length scales relevant for clinical applications. We release our code to the public domain, together with a detailed description of the implementation and several examples, with the hope of usage and futher development by the community. A justification for the included algorithms and the biological models was obtained in previous publications, here we summarize the technical aspects following the workflow of a typical simulation procedure