Rods and cones coexist peacefully in healthy retinas. Both types of cells occupy the same layer of tissue and send signals when they detect light, which is the first step in vision.
The incurable eye disease Retinitis Pigmentosa, however, reveals a codependent relationship between the two that can be destructive. When flawed rods begin to die, otherwise normal cones follow them to the grave, leading to blindness. A new study might explain why.
Data published online in Nature Neuroscience Dec. 7 suggest the cones are starving to death. As rods disappear, the structure of the retina breaks down. This might disrupt the connections between the cones and their source of nutrients.
“This is the first study linking cone death in Retinitis Pigmentosa to a metabolic problem that suggests starvation,” says senior author Constance Cepko, an HMS professor and investigator with Howard Hughes Medical Institute. “If we can find a way to supply nutrients to the cones, we might be able to preserve daylight vision in patients.”
Active in bright light, cones allow us to perceive color and fine details. Conversely, rods allow us to see in dim light. The untrained eye cannot distinguish between the two types of cells, which grow side-by-side. Both rods and cones have a protrusion that has many membranous discs, resembling a stack of cookies. A cone stack is half the height of a rod stack. Stacks emanating from both types of cells get clustered together, like Oreos on a plate. The entire plate gets covered in “plastic,” with the flexible plastic reaching down to touch each stack. In the eye, this plastic consists of a giant retinal pigment (RPE) cell, which supplies nutrients to the rods and cones on its plate.
With this structure in mind, researchers have proposed a variety of hypotheses to explain the loss of cones in patients with mutations in rod-specific genes. For example, some teams have suggested that rods produce a chemical cones need to survive. But the data didn’t quite fit the proposed models.
Cekpo’s team took a fresh approach to the problem. Postdoctoral researcher Claudio Punzo gathered four strains of mice, each with a different rod-specific mutation and a different rate of disease progression. He discovered an interesting pattern. Cone death always began after the major phase of rod death.
Punzo analyzed gene expression before and after this point in each strain. During the cone death phase, 230 genes were always expressed at higher levels. Sleuthing revealed that 34.9 percent of those play a role in cellular metabolism, including 12 genes in the insulin/mTOR pathway.
mTOR serves as a signaling hub, gathering information about the environment and helping the cell to decide whether it has enough nutrients to make new proteins. Punzo now had a lead. Further experiments suggested the cones weren’t getting enough glucose. Not only did they express high levels of a protein that allows the cell to take up more glucose, but the cones survived longer when Punzo tricked them into thinking they had enough glucose by injecting the mice with insulin.
“Apparently, the cones caught onto our trick,” says Punzo. “After surviving longer than usual, they started to die in droves.”
Cepko and Punzo say the new hypothesis makes sense. Rods outnumber cones by more than 20 to 1. The RPE cells sag when too many rods disappear, as the plastic over that plate of Oreo cookies droops when too many stacks are missing. The structural change likely disturbs the contacts between RPE cells and cones, impeding the flow of nutrients to the cones.
“This points us in a new direction,” says Cepko. “We’re currently exploring ways to boost nutrient levels in the cones. Perhaps someday we can help Retinitis Pigmentosa patients maintain their daylight vision for at least a bit longer than they otherwise would.”
This research is supported by the National Institutes of Health, the Macular Research Foundation, The Foundation for Retinal Research, Merck and the European Molecular Biology Organization.
Alyssa Kneller | Newswise Science News
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy