Microglia circadian disruption in progression of diabetic retinopathy

Brief Lay Background

Almost all people with diabetes will develop some form of diabetic retinopathy as they get older with the disease.

Diabetic retinopathy is a form of sight loss that can develop in anybody with type 1 or type 2 diabetes. It is caused by damage to blood vessels supplying the retina - the light-sensitive layer at the back of the eye.

It is the most common cause of sight loss among working-age adults in the UK, and is set to increase with the rising rate of diabetes.

What problem/knowledge gap does it help address

Scientists have discovered that diabetes affects the body’s circadian rhythm. The circadian rhythm is the internal clock in our brain that regulates our wake and sleep cycles by responding to light in our environment. Our body has a circadian rhythm, and so does each and every one of our cells.

This small grant funded with Diabetes UK will explore how the circadian rhythm affects inflammation in the retina – which scientists think is a key process in diabetic retinopathy.

It will explore how diabetes affects the circadian rhythm of inflammatory cells called microglia, which become activated in diabetic retinopathy.

Aim of the research project

To determine how diabetes disrupts the circadian rhythm of inflammatory microglial cells in diabetic retinopathy.

Key procedures/objectives

1. Determine whether diabetes disrupts the usual circadian pattern of microglia activation in mice. Mice with and without diabetes will be exposed either to normal periods of light and dark, or kept solely in the dark. Dr Beli will then measure the activation levels of microglia under these different conditions.
2. Understand how high blood glucose affects microglia circadian rhythms. Dr Beli will grow microglia in different levels of glucose and measure the activity of genes involved in regulating the circadian rhythm. This will provide direct evidence that glucose levels interfere with the internal clock in microglia.
3. Test whether the cell’s circadian clock is important in inflammation in diabetes. Dr Beli will delete a gene in microglia that makes the clock defective, and see how this affects inflammation when blood glucose levels are high. This will provide proof that a defective clock can to the inflammation that can cause diabetic retinopathy. 

Potential impact on people with sight loss

This project is the first to explore the link between the circadian rhythm and inflammation in the retina in diabetes. It will provide invaluable insights into the mechanisms that cause diabetic retinopathy and could ultimately pave the way to new treatments that prevent sight loss.