Philipp Mueller

Disease expression in autosomal recessive retinal dystrophy associated with mutations in the DRAM2 gene

PURPOSE To determine the disease course of retinal dystrophy caused by recessive variants in the DRAM2 (damage-regulated autophagy modulator 2) gene. METHODS Sixteen individuals with DRAM2-retinopathy were examined (six families; age range, 19-56 years, includes one pre-symptomatic case). The change in visual acuity over time was studied, and electrophysiology (n = 6), retina-tracking perimetry (n = 1), fundus autofluorescence (FAF) imaging (n = 6), and optical coherence tomography (OCT; n = 12) were performed. RESULTS All symptomatic patients presented with central visual loss (15/15) unaccompanied either by nyctalopia or light-hypersensitivity; most (11/15) developed symptoms in the third decade of life. A granular macular appearance, often with associated white/yellow dots, was an early fundoscopic feature. There was an ill-defined ring of hyperautofluorescence on FAF. Optical coherence tomography revealed loss of the ellipsoid zone perifoveally in a 19-year-old pre-symptomatic individual. The central atrophic area enlarged over time and fundoscopy showed peripheral degeneration in seven of the nine individuals that were examined ≥ 10 years after becoming symptomatic; some of these subjects developed nyctalopia and light hypersensitivity. Electrophysiology revealed generalized retinal dysfunction in three of the five individuals that were tested ≥ 10 years after becoming symptomatic. CONCLUSIONS Patients with DRAM2-retinopathy are typically asymptomatic in the first two decades of life and present with central visual loss and a maculopathy. A faint hyperautofluorescent ring on FAF can be a suggestive feature. The retinal periphery is frequently affected later in the disease process. Photoreceptor degeneration is likely to be the primary event and future studies on DRAM2-retinopathy are expected to provide important insights into retinal autophagy.

Operating a large-area MPP-CCD with antiblooming

We describe the performance of a 2k X 2k, 15 (mu) pixel, buried channel MPP-CCD (Loral FA2048) using different operating modes and the implementation of an anti-blooming clocking technique. The CCD is part of a camera system developed at Bonn University for astronomical wide field photometry and polarimetry. Besides two basic operating modes (partially and non-inverted mode) the multi pinned phase (MPP) design additionally allows a totally inverted mode providing the strongest reduction of dark current. The disadvantage is a low full well capacity of 120000 electrons/pixel which only depends on the small implanted potential offset. As an example for optimization by choosing adequate voltages we show how this original full well capacity can be raised almost by a factor of 2 without decreasing the quality of the read-out. Finally we discuss the physical understanding and technical implementation of anti-blooming and its future application in astronomical photometry. Using clocking rates up to 2 kHz we achieve a minimum anti-blooming efficiency of 400 electrons/sec/pixel/Hz and a low spurious charge generation further reduced by using ramps or intermediate steps in the anti-blooming clocking waveforms.

Performance tests of a DIVA-CCD: before and after proton irradiation

The E2V CCD42-20 NIMO type CCD was tested in view of its use for the german astrometric satellite mission DIVA. As in other astrometric missions (FAME, GAIA) the CCDs will be operated in TDI mode synchronous with the stars drifting across the detectors. At the expected operating temperature, around -30C to -50C, the dark current performance is an important parameter. Radiation induced degradations with respect to dark current and CTE are of particular concern, too. We find that TDI operation reduces the dark current by a factor of ≈30 near the DIVA satellite TDI clock rate (1.4 msec). The detector was irradiated with soft protons, in a first run, with rather weak doses of up to an equivalent 10 MeV fluence of 1.6×108 protons/cm2. The increase in dark current is quite small (4% to 5% maximum at -40C) but seems to vary with temperature (e.g. 2% at -60C). The CTE degradation shows a linear dependance on the radiation dose and the CTE gets worse if the detector temperature gets lower (e.g. for the highest dose: 0.999 98 at -60C and 0.999 95 at -100C). Vertical and horizontal deferred charge patterns show a significant difference. The total mission dose will be about 10x higher and the dark current and CTE values are tentatively extrapolated. The results of this study shall serve as a basis for further irradiation experiments combined with laboratory simulations and numerical modelling. During the course of this study the DIVA project had to be stopped due to lack of funding. But our results are applicable equally well to the proposed SMEX mission AMEX which is based on the DIVA concept.