Targeting Connexin and Pannexin channel signalling in Diabetic Retinopathy

Reference: SHLS20042

Diabetic retinopathy (DR) is a microvascular consequence of diabetes mellitus (both Type 1 and Type 2) affecting more than a third of diabetics (affecting an estimated 100million people worldwide). DR results in progressive irreversible deterioration of the tiny blood vessels within the retina as a result of chronic hyperglycemia, leading to severe damage of the retinal microvasculature and associated vision problems including blindness (approximately a third of DR is sight threatening). Diabetes can trigger DR by increasing the production of free radicals from diverted glucose metabolism pathways including non-enzymatic glycosylation, the hexosamine pathway, activation of Protein KinaseC and poly (ADP-ribose) polymerase pathways. Oxidative stress and inflammation also contribute to the pathogenesis of DR. Cell to cell communication via Connexin and Pannexin channels is central to maintaining cellular homeostasis and these events are dysregulated in the diabetic state and during inflammation. Aberrant opening of these channels results in release of ATP impacting on downstream purinergic and inflammatory signalling pathways. Thus strategies to inhibit hemichannel signalling receive wide spread attention and a range of peptide and siRNA strategies are available to inhibit channel behaviour. The Hyperglycaemic state can also impact on the post-translational modification of these proteins, in particular phosphorylation (connexins) and glycosylation (pannexins). The subsequent alterations in the function of these proteins, that can act as ‘signalling hubs’ for a wide range of cellular activities, remains to be explored in DR leading to new therapeutic strategies.

Aims: The study will use in vitro and in vivo models to study the role of connexins and pannexins in the development of diabetic retinopathy.

The candidate will join internationally networked research teams in the study of retinal disease and the role of Connexins and Pannexins in Health and disease.

Research Group: https://www.gcu.ac.uk/hls/research/researchgroups/molecularmechanismsofdiabetes/

And https://www.gcu.ac.uk/hls/research/researchgroups/visionresearch/

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