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Diurnal clearance phagocytosis by the retinal pigment epithelium (RPE) is a conserved efferocytosis process whose binding step is mediated by αvβ5 integrin receptors. Two related annexins, A5 (ANXA5) and A6 (ANXA6), share an αvβ5 integrin-binding motif. Here, we report that ANXA5, but not ANXA6, regulates the binding capacity for spent photoreceptor outer segment fragments or apoptotic cells by fibroblasts and RPE. Similar to αvβ5-deficient RPE, ANXA5−/− RPE in vivo lacks the diurnal burst of phagocytosis that follows photoreceptor shedding in wild-type retina. Increasing ANXA5 in cells lacking αvβ5 or increasing αvβ5 in cells lacking ANXA5 does not affect particle binding. Association of cytosolic ANXA5 and αvβ5 integrin in RPE in culture and in vivo further supports their functional interdependence. Silencing ANXA5 is sufficient to reduce levels of αvβ5 receptors at the apical phagocytic surface of RPE cells. The effect of ANXA5 on surface αvβ5 and on particle binding requires the C-terminal ANXA5 annexin repeat but not its unique N-terminus. These results identify a novel role for ANXA5 specifically in the recognition and binding step of clearance phagocytosis, which is essential to retinal physiology. [ABSTRACT FROM AUTHOR]

Background: QT interval on the surface electrocardiogram reflects the time for repolarization of myocardium. Prolongation of rate-corrected QT interval, QTc is strongly associated with sudden cardiac death. Recent studies using novel techniques on beat-to-beat QT interval variability have shown that an increase in QT interval variability is associated with increased sympathetic activity and is a predictor of sudden cardiac death. We studied QT variability in patients with congestive cardiac failure, as it is associated with an increase in cardiac sympathetic activity and also sudden death., Methods and Results: We compared beat-to-beat heart rate and QT interval data in 2 3 patients with congestive cardiac failure and 19 age-matched normal controls. The electrocardiographic data were acquired in lead II configuration at a sampling rate of 1000 Hz. Heart rate variability was found to be significantly lower while QT variability measures were significantly higher in patients compared to controls. QTvi (a common log ratio of QT variability normalized for mean QT interval squared divided by heart rate variability normalized for mean heart rate squared) was also significantly higher in patients compared to controls. Clinical improvement in some of these patients is associated with a decrease in QTvi, due mainly to an increase in cardiac vagal function., Conclusions: Our results suggest a decrease in cardiac vagal and an increase in cardiac sympathetic functions in patients with congestive cardiac failure. QTvi may prove to be a useful surrogate end point to evaluate treatment effect in these patients.