Study reveals functional similarity between healthy retinal cell and tumor cell

How does a healthy retina cell look like a tumor cell? It diverts a chemical reaction producing energy to produce molecular building blocks. When tumor cells do, they use the basics to grow and spread cancer. But when the cells of the retina do, they renew the membranes of the photoreceptors that keep our vision clear.

Jianhai Du, researcher at West Virginia University, badyzes how the retina accomplishes this feat. His conclusions are published in the latest edition of Proceedings of the National Academy of Sciences.

"We consume glucose and use it as a source of major energy," said Du, an badistant professor in the Department of Biochemistry of the Faculty of Medicine and Department of Ophthalmology and Vision Sciences. . Through a multi-stage chemical process, almost every healthy cell in our body wants to turn this glucose into a fuel that mitochondria – essentially cell boilers – can burn to produce energy. Less than 20% of glucose is used to make raw materials for new cells.

"But in tumor cells, it's almost the opposite," Du said. Tumor cells do everything they can to thwart the chemical reactions that would normally turn glucose into energy. Instead, they turn most of the glucose into the basic components of cancer.

"It's like they're building different houses.When you're building houses, you need basic materials like wood and concrete.When cancers develop, they need membranes, lipids , nucleotides. "

Retina cells use glucose in the same way, but rather than using it to maintain and spread cancer, they use it to generate new outer segments of photoreceptors that replace old damaged segments.

Du and his research team have suspected that a specific protein, called Mitochondrial Pyruvate Carrier 1, plays a role in the retina's ability to remove glucose from the photoreceptor parts. MPC1 is essential for obtaining a glucose derivative – called pyruvate – in cell "boiler rooms", where it can be burned to fuel the cell. "But in almost all cancer cells, MPC1 is reduced because cells do not want to displace pyruvate in mitochondria," Du said.

Scientists used animal models to study whether – and how – MPC1 and retinal health were related. They also tested whether the small amount of pyruvate entering the mitochondria of the retina is important.

The team has removed all MPC1 from some of their animal models. In the rest of the models, they remained intact. "It turns out that the small amount of glucose used in mitochondria is essential for mitochondrial function, photoreceptor function, and viability," Du said.

The researchers observed that models deficient in MPC1 had a dramatic impairment of vision. Compared to their counterparts with a typical expression of MPC1, their photoreceptors also function less than half at all light intensities.

The team also found that depletion of MPC1 caused retinal degeneration. In addition, he damaged the retinal mitochondria structure of "very, very unique," Du said.

"An important factor in the development of age-related macular degeneration is the mitochondria do not work very well.But people do not know exactly what causes it and there is still no treatment ", did he declare. Du's research could provide insight into how this misunderstood disease manifests itself in patients and how physicians can treat it. He and his colleagues are conducting experiments to determine if fat can be used as an alternative fuel source for retinal mitochondria that can not use glucose properly.

Du also plans to study what happens when MPC1 is blocked cell by cell. "In this project, we have blocked all the retina, but in the next we want to block the photoreceptors or glial cells to see how small molecules cross, we want to address the interactions between cells." Such a project could have an impact beyond the diagnosis and treatment of eye diseases. It may even allow neuroscientists to better understand how brain cells interact.