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INTERPERICYTE TUNNELING NANOTUBE CONNECTING TWO DISTAL VESSELS. ALARCON-MARTINEZ ET AL NATURE 585 (7823) 91-95, 2020
CERA is using pioneering experimental methods to uncover previously unknown structures in the retina
The Centre for Eye Research Australia (CERA) in Melbourne is noted as one of the top ophthalmology research centres in the world. Its newly established Visual Neurovascular Research Unit is using pioneering experimental methods to uncover previously unknown structures in the retina.
From pre-clinical research through to patient trials, the researchers are looking at ways to better understand glaucoma and improve diagnosis so that they can develop new treatments. This new Unit, led by Dr Luis Alarcon-Martinez, is investigating the mechanisms which control blood flow to the retina, a complex layer of cells at the back of the eye.
When our vision works correctly, light is picked up in the retina and turned into electrical signals which are transmitted to the brain by millions of retinal ganglion cells. These cells transmit visual information to the brain through long nerve fibres, known as axons, which bundle together to make up the optic nerve.
Retinal ganglion cells require an adequate supply of oxygen and nutrients from surrounding blood vessels to function properly. Inadequate blood supply can damage these cells and lead to vision loss. The research aims to gain a better understanding of how exactly blood is distributed in the retina in order to prevent damage and preserve sight.
While it is known that interruption of blood supply is found in diseases such as glaucoma, diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration, at present there is only limited understanding of the exact mechanisms that control the distribution of blood in the retina.
The team will be investigating the processes that enable neurons to communicate with blood vessels. That neurons need more energy, and that the vessels supply the elements to produce it is known, but what is not known currently is exactly how that happens.
While this lack of understanding might come as a surprise, according to Dr Alarcon-Martinez there are two good reasons for it. The first is because the processes are happening at a very small scale: that of single nerve cells and capillaries. The second is that they need to be observed in living organisms.
The researchers are trying to understand the dynamic processes – to see the blood running into the vessels, and the nerve cells being activated. Until recently, there wasn’t the technology to be able to look at such small environments in the retinas of living organisms.
Thanks to work by a team at the University of Montreal – which Dr Alarcon-Martinez was a part of – a new experimental set-up was developed to achieve this. Using cutting-edge two-photon microscopy, they were able to observe these processes in living organisms at high levels of resolution, the first researchers to do so.
They discovered a previously unknown mechanism by which cells in the retina communicate with one another to regulate blood supply. Embedded within the capillaries are pericytes – cells that can control the amount of blood passing through the capillaries by dilating or contracting them.
By observing the vascular changes in the retinas of mice, the team showed that pericytes use very thin tubes, or nanotubes, to communicate with one another and supply blood where it is most needed.
Their study also showed that capillaries lose their ability to regulate blood supply when these nanotubes are damaged, leading to detrimental effects on neurons and the functioning of the retina. This suggests that the interruption of blood supply found in retinal neurodegenerative diseases might be a result of these nanotubes breaking down. The study was published in Nature in 2020.
Next at the new Unit is research to get a better understanding of the dynamics between these nanotubes, the neurons, and vessels. When a neuron is activated, things change. But they want to know exactly what the neuron is releasing to make these nanotubes work.
If the research helps to develop strategies to prevent or treat retinal neurodegenerative diseases, it could also be used for other neurodegenerative diseases such as Alzheimer’s disease and strokes.
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