Why do nerve cells and blood vessels stop working together in diabetes?

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Graham McGeown
  • Institute: Queen’s University Belfast
  • Region: Northern Ireland
  • Start date: October 2010
  • End Date: October 2013
  • Priority:
  • Eye Category:


Active nerve cells need an extra supply of oxygen and nutrients from the blood. Usually, the nerve cells in the light-sensitive part of the eye (the retina) can control the amount of blood flow they get by sending signals to nearby blood vessels. The blood vessel walls respond to the signals by becoming wider or narrower as needed, depending on ow active the nerve cells are. But these signals (known as retinal neurovascular coupling) don’t work normally in people with diabetes. The problems can start before the stage at which diabetic retinopathy is currently diagnosed, but they may play a part in permanent damage to the retina.

In this project the student is comparing what happens in the retinas of rats with and without the symptoms of diabetes. They will use a microscope that can measure the width of blood vessels and will also investigate what happens inside the cells when the nerve cells, supporting cells (called glial cells) and the muscle in blood vessel walls are activated. The aim is to find out at what point retinal neurovascular coupling goes wrong. Results from the project could give us an early biological marker, or ‘biomarker’ that could help predict the course of an individual’s condition, or give us a new target for developing treatment to delay or reduce the effect of diabetic retinopathy.

  • Scientific summary

    Cellular mechanisms responsible for disruption of retinal neurovascular coupling in diabetes mellitus.

    Retinal neurovascular coupling, which increases blood flow by dilating retinal microvessels in response to neuronal activity, is impaired in diabetic patients. This impairment can precede overt retinopathy but is correlated with the level of retinopathy when present. The proposed study addresses the mechanisms responsible for this functional abnormality for the first time.

    Changes in retinal vessel diameter are being imaged in intact retina using infrared to avoid photoreceptor activation. The cellular basis of neurovascular coupling is being mapped functionally using stimuli to selectively activate photoreceptors (light), neurones (focal electrical stimulation or neurotransmitter application), glial cells (focal electrical stimulation, neurotransmitters, photolytic release of intraglial Ca2+), or blood vessels (eg arachidonic acid (AA) metabolites). Glial Ca2+-signals and the direct effect of putative gliovascular signals on isolated pressurised retinal arterioles are being recorded. Responses are being compared for diabetic (streptozotocin rat model) and age-matched control tissues in order to determine the site of signaling faults (eg neuroglial or gliovascular transmission).

    The team has shown that the BK ion channel activity is decreased in the myocytes of diabetic retinal arterioles due to reduced expression of the beta1-subunit. This may reduce vascular responses to AA metabolites, which often target this channel. The team is also investigating expression and distribution of other candidate signalling molecules at transcript and protein level to identify the molecular basis of signal failure. The work will provide not just an understanding of how diabetes interferes with retinal blood flow regulation but also improved experimental tools for the investigation of neurovascular coupling in the eye.

  • Research update

    In this study the team discovered a new process that could contribute to getting diabetic retinopathy. They studied support cells – called Muller glial cells – that are a vital part of the way that nerve cells in the retina send signals to the blood vessels. Results showed that Muller glial cells in the diabetic retina were not able to break down toxic proteins known as ‘advanced lipoxidation endproducts’. This is important because more of the chemicals that lead to these toxic proteins are produced by the body in diabetics. If the toxins aren’t broken down and cleared away, they can potentially build-up inside cells and cause damage. The team was excited to find that a drug that binds together with the toxic proteins was able to reduce the effect of diabetes in the eye. There’s still lots to understand, but this could lead to a new treatment to slow or delay diabetic retinopathy.

  • Publications