Retinitis Pigmentosa (RP) begins with the death of rod photoreceptors and is slowly followed by a gradual loss of cones and a rearrangement of the remaining retinal neurons. Clusterin is a chaperone protein that protects cells and is involved in various pathophysiological stresses, including retinal degeneration. Using a well-established transgenic rat model of RP (rhodopsin S334ter), we investigated the effects of clusterin on rod photoreceptor survival. To investigate the role of clusterin in S334ter-line3 retinas, Voronoi analysis and immunohistochemistry were used to evaluate the geometry of rod distribution. Additionally, immunoblot analysis, Bax activation, STAT3 and Akt phosphorylation were used to evaluate the pathway involved in rod cell protection. In this study, clusterin (10μg/ml) intravitreal treatment produced robust preservation of rod photoreceptors in S334ter-line3 retina. The mean number of rods in 1mm2 was significantly greater in clusterin injected RP retinas (postnatal (P) 30, P45, P60, & P75) than in age-matched saline injected RP retinas (P<0.01). Clusterin activated Akt, STAT3 and significantly reduced Bax activity; in addition to inducing phosphorylated STAT3 in Müller cells, which suggests it may indirectly acts on photoreceptors. Thus, clusterin treatment may interferes with mechanisms leading to rod death by suppressing cell death through activation of Akt and STAT3, followed by Bax suppression. Novel insights into the pathway of how clusterin promotes the rod cell survival suggest this treatment may be a potential therapeutic strategy to slow progression of vision loss in human RP.

The institution of massive transfusion protocols (MTPs) has improved the timely delivery of large quantities of blood products and improves patient outcomes. In recent years, the cost of blood products has increased, compounded by significant blood product shortages. There is practical need for identification of a transfusion volume in trauma patients that is associated with increased mortality, or a threshold after which additional transfusion is futile and associated with nonsurvivability. This transfusion threshold is often described in the setting of an ultramassive transfusion (UMT). There are few studies defining what constitutes amount or outcomes associated with such large volume transfusion. The purpose of this narrative review is to provide an analysis of existing literature examining the effects of UMT on outcomes including survival in adult trauma patients and to determine whether there is a threshold transfusion limit after which mortality is inevitable. Fourteen studies were included in this review. The data examining the utility of UMT in trauma are of poor quality, and with the variability inherent in trauma patients, and the surgeons caring for them, no universally accepted cutoff for transfusion exists. Not surprisingly, there is a trend toward increasing mortality with increasing transfusions. The decision to continue transfusing is multifactorial and must be individualized, taking into consideration patient characteristics, institution factors, blood bank supply, and most importantly, constant reevaluation of the need for ongoing transfusion rather than blind continuous transfusion until the heart stops.