Regulatory regions of the paraoxonase 1 (PON1) gene are associated with neovascular age-related macular degeneration (AMD)

Physiological stress response and oxidative damage are factors for aging processes and, as such, are thought to contribute to neovascular age-related macular degeneration (AMD). Paraoxonase 1 (PON1) is an enzyme that plays an important role in oxidative stress and aging. We investigated association of DNA sequence variants (SNP) within the upstream regulatory region of the PON1 gene with neovascular AMD in 305 patients and 288 controls. Four of the seven tested SNPs (rs705379, rs705381, rs854573, and rs757158) were more frequently found in AMD patients compared to controls (P = 0.0099, 0.0295, 0.0121, and 0.0256, respectively), and all but one (SNP rs757158) are in linkage disequilibrium. Furthermore, haplotype TGGCCTC conferred protection (odds ratio (OR) = 0.76, (CI) = 0.60-0.97) as it was more frequently found in control individuals, while haplotype CGATGCT increased the risk (OR = 1.55, CI = 1.09-2.21) for AMD. These results were also reflected when haplotypes for the untranscribed and the 5'untranslated regions (5'UTR) were analyzed separately. To assess haplotype correlation with levels of gene expression, the three SNPs within the 5'UTR were tested in a luciferase reporter assay. In retinal pigment epithelium-derived ARPE19 cells, we were able to measure significant differences in reporter levels, while this was not observed in kidney-derived HEK293 cells. The presence of the risk allele A (SNP rs705381) caused an increase in luciferase activity of approximately twofold. Our data support the view that inflammatory reactions mediated through anti-oxidative activity may be relevant to neovascular age-related macular degeneration

Optical Transponders

The first commercial 10 - Gb/ s transponders, deployed in the mid 1990s, were based on a very simple modulation technique, i. e., a binary light intensity modulation with envelope detection by a single photodiode. To extend the fiber capacity, bandwidth-efficient modulation techniques such as duobinary line coding and multilevel intensity-modulation formats gained popularity in optical communications in the late 1990s. In the following years, the use of differential phase modulation in combination with interferometric detection allowed the transponder data rates to be increased up to 40Gb/s. However, despite all improvements, the system performance of these 40 - Gb/ s solutions was still not on par with state-of-the art 10 - Gb/ s systems at that time. With the advent of coherent detection, things suddenly changed and transmission rates of 100Gb/s and beyond could soon be achieved, thanks to the use of high-order modulation formats and advanced digital signal-processing techniques. In this chapter, the configuration and performance of the most common transmitter and receiver combinations that are currently used in optical transmission systems will be described, including an overview of transponder types and their hardware architectures. Finally, relevant standards will be discussed and pluggable optical transceiver modules used in modern transponder implementations will be explained