Survival or death: a dual role of autophagy in stress-induced pericyte loss in diabetic retinopathy

Aims/hypothesis
Intra-retinal extravasation and modification of LDL have been implicated in diabetic retinopathy: autophagy may mediate these effects.
Methods
Immunohistochemistry was used to detect autophagy marker LC3B in human and murine diabetic and non-diabetic retinas. Cultured human retinal capillary pericytes (HRCPs) were treated with in vitro-modified heavily-oxidised glycated LDL (HOG-LDL) vs native LDL (N-LDL) with or without autophagy modulators: green fluorescent protein–LC3 transfection; small interfering RNAs against Beclin-1, c-Jun NH(2)-terminal kinase (JNK) and C/EBP-homologous protein (CHOP); autophagy inhibitor 3-MA (5 mmol/l) and/or caspase inhibitor Z-VAD-fmk (100 μmol/l). Autophagy, cell viability, oxidative stress, endoplasmic reticulum stress, JNK activation, apoptosis and CHOP expression were assessed by western blots, CCK-8 assay and TUNEL assay. Finally, HOG-LDL vs N-LDL were injected intravitreally to STZ-induced diabetic vs control rats (yielding 50 and 200 mg protein/l intravitreal concentration) and, after 7 days, retinas were analysed for ER stress, autophagy and apoptosis.
Results
Intra-retinal autophagy (LC3B staining) was increased in diabetic vs non-diabetic humans and mice. In HRCPs, 50 mg/l HOG-LDL elicited autophagy without altering cell viability, and inhibition of autophagy decreased survival. At 100–200 mg/l, HOG-LDL caused significant cell death, and inhibition of either autophagy or apoptosis improved survival. Further, 25–200 mg/l HOG-LDL dose-dependently induced oxidative and ER stress. JNK activation was implicated in autophagy but not in apoptosis. In diabetic rat retina, 50 mg/l intravitreal HOG-LDL elicited autophagy and ER stress but not apoptosis; 200 mg/l elicited greater ER stress and apoptosis.
Conclusions
Autophagy has a dual role in diabetic retinopathy: under mild stress (50 mg/l HOG-LDL) it is protective; under more severe stress (200 mg/l HOG-LDL) it promotes cell death.

Video anomaly detection in real-time on a Power-Aware Heterogeneous Platform

FPGAs and GPUs are often used when real-time performance in video processing is required. An accelerated processor is chosen based on task-specific priorities (power consumption, processing time and detection accuracy), and this decision is normally made once at design time. All three characteristics are important, particularly in battery-powered systems. Here we propose a method for moving selection of processing platform from a single design-time choice to a continuous run time one.We implement Histogram of Oriented Gradients (HOG) detectors for cars and people and Mixture of Gaussians (MoG) motion detectors running across FPGA, GPU and CPU in a heterogeneous system. We use this to detect illegally parked vehicles in urban scenes. Power, time and accuracy information for each detector is characterised. An anomaly measure is assigned to each detected object based on its trajectory and location, when compared to learned contextual movement patterns. This drives processor and implementation selection, so that scenes with high behavioural anomalies are processed with faster but more power hungry implementations, but routine or static time periods are processed with power-optimised, less accurate, slower versions. Real-time performance is evaluated on video datasets including i-LIDS. Compared to power-optimised static selection, automatic dynamic implementation mapping is 10% more accurate but draws 12W extra power in our testbed desktop system.