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Colin Green; Connexin 43 in corneal and retinal injury and disease. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
The two hemichannels (connexons) that make up a gap junction channel need to have low opening probability prior to docking with a neighboring cell. Open hemichannels form a large, relatively non-selective membrane channel directly exposing the cell cytoplasm to the extracellular milieu. Under injury and disease conditions gap junction coupling may be reduced, but both Connexin 43 expression and hemichannel opening are increased. The hemichannel has therefore been referred to as a pathological pore and it is a key component in the inflammasome pathway during both its initiation and propagation. In this seminar the effect of pathological opening of connexin hemichannels in ocular injury and the benefits of intervention are described. In a rat cornea photorefractive keratectomy model, down regulation of Connexin 43 expression prevents edema and myofibroblast activation. In a rabbit trabeculectomy model, Connexin 43 down regulation reduces inflammation and scarring which can result in cannula block. In the bright light retinal injury model intravitreal injection of connexin hemichannel blocking peptides reduces inflammation and significantly improves functional outcomes (electroretinograms). In a rat retinal-ischemia reperfusion model systemic delivery or intravitreal injection of hemichannel blocking peptides prevents loss of vascular integrity, reduces glial cell activation and cuts downstream retinal ganglion cell (neuron) loss by over two thirds. These data, correlated with ex vivo human donor tissue analysis, further indicates that loss of vascular integrity may be common component in ocular disease, including retinal pigment epithelium loss, age related macular degeneration and diabetic retinopathy. Finally, instances where Connexin 43 modulation has resulted in sight saving outcomes in humans with persistent trabeculectomy scarring or severe ocular surface burns, which were unresponsive to established therapy, will be presented.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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