Ruben N. Sanchez

Nuclear factor-κB p65 and upregulation of interleukin-6 in retinal ischemia/reperfusion injury in rats

Abstract We previously demonstrated that endogenous interleukin-6 (IL-6) is upregulated and may be neuroprotective after retinal ischemia. The purpose of this study is to investigate the role of nuclear factor kappa-B (NF-κB) in regulating IL-6 expression after ischemia. NF-κB p65 mRNA levels were significantly elevated between 2 and 12 h after the insult. A high number of NF-κB p65 positive cells were detected in the inner retina at 12 h after ischemia. Activated nuclear NF-κB p65 and IL-6 were colocalized in cells, which were also marked by a microglial/phagocytic cell marker (ED1) in the inner retina. Carbobenzoxy- l -leucyl- l -leucyl- l -leucinal (MG-132, a proteasome inhibitor, which inhibits IκB degradation and hence prevents the activation and translocation of NF-κB into the nucleus) abolished the increase in NF-κB p65 mRNA levels after the insult, while there was no effect by helenalin (an inhibitor which inhibits NF-κB activity by alkylation of the p65 subunit, thereby blocking its binding to the target DNA). However, MG-132 and/or helenalin significantly diminished the increase in IL-6 mRNA levels after the insult. Small interfering RNAs (siRNAs, inhibit target gene expression through the sequence-specific destruction of the target messenger RNA) against NF-κB p65 significantly reduced the increase in NF-κB p65 mRNA levels as well as IL-6 mRNA levels after ischemia. The number of retinal ganglion cells (RGCs) was also significantly decreased using the inhibitors of NF-κB compared with those of the controls after ischemia. These findings support the hypothesis that upregulation of endogenous retinal IL-6 in retinal I/R injury in microglial/phagocytic cells is controlled predominantly by NF-κB p65.

Death associated with an indwelling orbital catheter.

We report a case of a 38-year-old woman who underwent revision of an orbital implant. A flexible indwelling orbital catheter was placed for postoperative anesthesia. Marcaine, administered to the patient through the 5.25-inch catheter while the patient was at home, led to respiratory arrest. After unsuccessful resuscitation, the patient died. At autopsy, it was noted that the catheter passed through the superior orbital fissure, with evidence of injection of marcaine in the subarachnoid space. This patient had signs and symptoms of Stickler syndrome. This leads us to believe that deficiencies in collagen II led to a weakness of the connective tissue surrounding the superior orbital fissure, leading to facilitated passage of the catheter into the subarachnoid space. This may be the first report of this type of outcome when using indwelling catheters for ophthalmic surgery. We recommend that placement of orbital indwelling catheters be performed in a controlled hospital setting.