Pericytes as instigators of microvascular dysfunction and neuronal hypoxic injury in diabetic ischaemia and neuropathy

In diabetes blood sugar levels in the body are elevated, which causes tissue damage. The most common complication is nerve damage, which typically occurs in the lower limbs and is the second greatest contributor to limb amputation worldwide. Nerve damage in diabetes occurs due to a reduction in nerve blood flow through capillaries, the smallest blood vessels. During diabetes nerve capillaries lose associated cells termed "pericytes", but how pericyte damage and loss contribute to reduced nerve blood flow and nerve injury is unknown. In diabetic blindness, similar pericyte loss is a key driver of retinal damage. In this fellowship, I will investigate the role pericyte injury plays in nerve damage through advanced imaging and electrophysiological techniques in animal models of diabetes, with confirmation in patient samples. I aim to further the understanding of diabetic nerve injury and highlight clinical targets to reduce the debilitating effects of this major socioeconomic problem.