[Imaging and molecular genetic diagnostics for the characterization of retinal dystrophies]. / Bildgebung und molekulargenetische Diagnostik zur Charakterisierung von Netzhautdystrophien.

Hereditary retinal dystrophies represent a genetically and clinically heterogeneous group of diseases. A comprehensive characterization constitutes functional and high-resolution multimodal imaging. With the advent of novel treatment options the detection of the underlying gene causing the disease is becoming more important. Technical advances in molecular genetic diagnostics enable a classification of retinal dystrophies depending on the specific genetic cause of the disease, which is important particularly against the background of newly emerging therapy approaches. Targeted next generation sequencing (NGS), in particular is now an efficient method to accomplish this and can be especially helpful to identify rare and potentially new disease-causing variants. For the interpretation of the molecular genetic results a close collaboration between ophthalmologists and geneticists is essential.

BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival.

The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca(2+) levels, suggesting an exhausted mitochondrial Ca(2+) buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca(2+) homeostasis in lymphocytes.

[Clinical applications of OCT angiography]. / Klinische Anwendungen der OCT-Angiographie.

BACKGROUND: Optical coherence tomography angiography (OCT-A) allows noninvasive, depth-selective visualization of retinal and choroidal vascular networks by detecting the endoluminal blood flow. This results in three-dimensional high-resolution images which are not possible by regular fluorescein angiography in this spatial resolution. Thus, OCT-A can be used to visualize the microperfusion of retinal and choroidal vessels and their alterations due to diverse pathologies and during the course of therapy. Based on several clinical case reports this article gives an overview of the wide range of applications of OCT-A. METHODS: The OCT-A images were obtained with the Spectralis OCT-2 prototype (Heidelberg Engineering, Heidelberg, Germany). This device provides an increased A scan rate of 70 kHz, which allows the generation of high-resolution OCT volume scans. RESULTS: The areas of application are manifold and include neovascular age-related macular degeneration, diabetic retinopathy, retinal vascular occlusion, inflammatory diseases and telangiectasia of various etiologies. The resulting images and their interpretation differ significantly from regular fluorescein angiography. Knowledge of these differences and of the limitations of this novel diagnostic device are of importance for its clinical application. For certain indications, OCT-A may be used as a substitute for invasive fluorescein angiography and provides more detailed information, particularly due to the absence of blockage phenomena, such as pooling or staining. CONCLUSION: The use of OCT-A allows visualization of the microperfusion of the retinal and choroidal vascular networks and their alterations due to diverse diseases in high resolution and with segmentation of different anatomical layers. The exact interpretation of the three-dimensional OCT-A images and their clinical application are currently under clinical evaluation.

[Pseudodominant inheritance of pseudoxanthoma elasticum]. / Pseudodominante Vererbung von Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a system disease due to mutations in the ABCC6 gene with characteristic alterations in the eyes, the skin and the cardiovascular system. Herein, we report on two families with PXE in two subsequent generations due to genetically confirmed pseudodominance. A literature review revealed that PXE due to mutations in ABCC6 follows an autosomal recessive inheritance and that disease manifestation in two subsequent generations is due to pseudodominance.