Could retinal endothelial- pericyte circadian coupling disruption play a role in diabetic retinopathy?
Brief plain language background
Diabetic retinopathy frequently leads to vision loss. One of the earliest events is the loss of pericytes, supporting cells that wrap around the blood vessels in the retina. Pericytes work closely with endothelial cells that line the vessels, to maintain the retinal blood supply. All cells in our body have tiny molecular clocks inside them, adapting their functions to the 24hr light/dark cycle. Thus, cells, like people, show circadian rhythms in their function, according to the time of the day. When these rhythms break down, the cells work sub optimally. Both pericytes and endothelial cells have their own clocks, but the pericyte clock gives the time to the vascular clock. When diabetic retinopathy causes pericytes to leave the vessels, the vascular clock is disrupted, influencing vascular function. This project examines this circadian cross-talk between pericyte and vascular clocks and investigates what happens when it breaks down in diabetes.
What problem/knowledge gap does it help address
Although the stages of diabetic retinopathy are well understood, the early events that damage the retina’s small blood vessels remain unclear. Lifestyle factors like disrupted sleep, shift work, and artificial light exposure, can interfere with the body’s internal clocks, potentially worsening diabetic complications. The circadian clock also help regulate blood vessel health, but its specific role in the retina is not well understood. Even less is known about how the clocks in different retinal cell types, like pericytes and endothelial cells, communicate with each other and stay in sync.
This project addresses this important knowledge gap by:
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investigating how circadian disruption in pericytes affects the retinal vascular rhythms.
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identifying pericyte signals influencing vascular circadian rhythms in diabetes.
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examining the impact of pericytes circadian clock on vascular function.
Uncovering these mechanisms could lead to brand new ways of protecting vision in people with diabetes, especially in the early stages of disease.
Aim of the project
To understand how two important cell types in the retina, pericytes and endothelial cells, communicate with each other using their body clocks (circadian rhythms) to keep retina’s blood vessels healthy.
Potential impact on people with sight loss
This research is relevant to all people with diabetes, especially those experiencing circadian disruption, a common issue affecting nearly 70% of the general population and even more among those with diabetes.
While still at an early stage, this study is a vital step toward understanding how body clocks help protect retinal blood vessels.
It could identify new treatment targets by revealing how disrupted timing signals between pericytes and endothelial cells contribute to diabetic retinopathy. Moreover, it may lead to new drugs, clock-based therapies (like chronotherapy), and lifestyle guidelines to improve sleep, light exposure, and routines that support retinal health.