Connexin43 gap junction protein is expressed in astrocytes and the vascular endothelium in the central nervous system. It is upregulated following central nervous system injury and is recognized as playing an important role in modulating the extent of damage. Studies that have transiently blocked connexin43 in spinal cord injury and central nervous system epileptic models have reported neuronal rescue. The purpose of this study was to investigate neuronal rescue following retinal ischaemia-reperfusion by transiently blocking connexin43 activity using a connexin43 mimetic peptide. A further aim was to evaluate the effect of transiently blocking connexin43 on vascular permeability as this is known to increase following central nervous system ischaemia. Adult male Wistar rats were exposed to 60 min of retinal ischaemia. Treatment groups consisted of no treatment, connexin43 mimetic peptide and scrambled peptide. Retinas were then evaluated at 1–2, 4, 8 and 24 h, and 7 and 21 days post-ischaemia. Evans blue dye leak from retinal blood vessels was used to assess vascular leakage. Blood vessel integrity was examined using isolectin-B4 labelling. Connexin43 levels and astrocyte activation (glial fibrillary acidic protein) were assessed using immunohistochemistry and western blot analysis. Retinal whole mounts and retinal ganglion cell counts were used to quantify neurodegeneration. An in vitro cell culture model of endothelial cell ischaemia was used to assess the effect of connexin43 mimetic peptide on endothelial cell survival and connexin43 hemichannel opening using propidium iodide dye uptake. We found that retinal ischaemia-reperfusion induced significant vascular leakage and disruption at 1–2, 4 and 24 h following injury with a peak at 4 h. Connexin43 immunoreactivity was significantly increased at 1–2, 4, 8 and 24 h post ischaemia-reperfusion injury co-localizing with activated astrocytes, Muller cells and vascular endothelial cells. Connexin43 mimetic peptide significantly reduced dye leak at 4 and 24 h. In vitro studies on endothelial cells demonstrate that endothelial cell death following hypoxia can be mediated directly by opening of connexin43 hemichannels in endothelial cells. Blocking connexin43 mediated vascular leakage using a connexin43 mimetic peptide led to increased retinal ganglion cell survival at 7 and 21 days to levels of uninjured retinas. Treatment with scrambled peptide did not result in retinal ganglion cell rescue. Pharmacological targeting of connexin43 gap junction protein by transiently blocking gap junction hemichannels following injury provides new opportunities for treatment of central nervous system ischaemia.

To compare the effect on the corneal endothelium of femtosecond laser-assisted cataract surgery and conventional phacoemulsification cataract surgery. Private clinic, Tasmania, Australia. Prospective comparative cohort study. Femtosecond laser-assisted cataract surgery (study group) or conventional phacoemulsification (control group) was performed. The central corneal thickness, central 3.0 mm corneal volume, volume stress index, and central endothelial cell density (ECD) were measured preoperatively and 1 day, 3 weeks, and 6 months postoperatively. The study group comprised 405 eyes and the control group, 215 eyes. Postoperative corneal edema was significantly less in the study group at 1 day and 3 weeks. However, the difference was negligible at 6 months. The study group had significant reductions in ECD loss compared with the control group [corrected] at 3 weeks but not at 6 months (6-month mean -150 cells/mm(2) ± 244 [SD] versus -149 cells/mm(2) ± 233). Eyes in the study group with laser-automated corneal incisions had greater endothelial cell loss at 6 months than eyes in the study group with manual corneal incisions and eyes in the control group (P<.0001). Eyes in the study group with zero effective phaco time and manually created corneal incisions had statistically significantly less endothelial cell loss at 6 months than the other groups (P<.0001). Femtosecond laser pretreatment for cataract surgery was associated with a significant reduction in early postoperative corneal edema and endothelial cell loss compared with conventional phacoemulsification; however, the difference diminished with time. Laser-automated corneal incisions seemed to adversely affect the corneal endothelial cells. No author has a financial or proprietary interest in any material or method mentioned.