For years, scientists have been aware that a lattice of blood vessels provides nourishment to the cells in the retina that enable us to see. However, the intricate process of how this structure is formed has been a mystery.
Recently, researchers have identified a new type of neuron that plays a role in guiding the formation of this lattice. This discovery has the potential to pave the way for new treatments for diseases linked to impaired blood flow in the eyes and brain.
Researchers at UC San Francisco have made a breakthrough discovery about a new type of neuron that plays a crucial role in its own formation. The findings, published in the May 23, 2024, issue of Cell, suggest that this discovery could pave the way for potential therapies for conditions related to impaired blood flow in the eyes and brain.
Dr. Xin Duan, an associate professor of ophthalmology and the senior author of the study, explained, “This is the first time anyone has observed retinal neurons forming precise 3-D lattices by making direct contact with blood vessels. This brings us closer to the possibility of repairing them when they’re damaged or rerouting them when they weren’t built correctly.”
ht in the first place.”
A protein that detects nearby cells
The scientists studied baby mice, whose eyes are still developing. Kenichi Toma, PhD, marked the retinal neurons closest to the blood vessels with a protein that glows green under ultraviolet light so he could watch the lattice as it formed.
The researchers then identified a group of neurons, known as perivascular neurons, that come into contact with and then surround developing blood vessels, guiding them to form the lattice. These perivascular neurons produce a protein called PIEZO2 that allows them to detect when the blood vessel is nearby.
They make contact with another cell.
In mice that were unable to produce PIEZO2, perivascular neurons could not maintain contact with blood vessels. This caused them to grow in a tangled, disorganized way, disrupting blood flow. As a result, the surrounding nerve cells degraded due to a lack of oxygen, making the mutant mice more susceptible to stroke-like injuries.
Duan’s research also revealed that these neurons play a role in guiding the formation of a similar network of blood vessels in the cerebellum. This part of the brain is responsible for coordination, language, and sense perception.
“The fact that we see this same pattern repeated in the Damage to this network of blood vessels in the brain may play a role in the development of various neurodegenerative diseases,” stated Toma. The team worked with developmental biologist Arnold Kriegstein, MD, PhD, to verify the presence of perivascular retinal neurons in humans. A 3-D visualization demonstrated how the network is formed, providing a new perspective that was previously limited by the use of only two-dimensional imaging techniques. The new approach, utilizing multiphoton microscopy, allowed Duan and Toma to benefit from cutting-edge technology developed by Tyson Kim, MD, PhD., a method for creating 3-D images of retinal blood networks without causing any disruption to the eye.
Kim and Toma worked together to develop rotating videos that captured the lattice from various perspectives and demonstrated how it deteriorated in the absence of PIEZO2.
Kim expressed, “We had been interested in collaborating for some time, and this was the perfect opportunity. It was really a merging of our individual passions.”
Protecting Neurons in a New Manner
These findings could potentially lead to new approaches for treating neurodegenerative diseases by ensuring that neurons, which require substantial energy, remain stable.A healthy blood supply is necessary for supporting the growth of neurons. Researchers like Xin Duan are trying to understand how to grow intricate networks of blood vessels to support neurons. This is an important question that they are working to answer.
