Study Proves Beneficial for Night Blindness

In a pair of related studies, scientists from the Florida campus of The Scripps Research Institute have uncovered several proteins that play a role in regulating cells' response to light – and the development of night blindness, a rare disease that abolishes the ability to see in dim light.

In the new studies, Scripps Research Associate Professor Kirill Martemyanov shows that a family of proteins known as Regulator of G protein Signaling (RGS) proteins plays an essential role in vision in a dim-light environment.

Dr. Martemyanov, who is a neuroscientist, began research to seek a better understanding of the fundamental mechanisms behind how we perceive light. In the process, his team discovered a pair of key molecules.

In a study published in the Proceedings of the National Academy of Scienceslast month, Dr. Martemyanov's team identified a pair of regulator proteins present in the main relay neurons of the retina, called ON-bipolar cells.

"The ON-bipolar cells provide an essential link between the retinal light detectors – photoreceptors and the neurons that send visual information to the brain," he said. "Stimulation with light excites these neurons by opening the channel that is normally kept shut by the G proteins in the dark."

The pair of regulator proteins facilitates the G protein inactivation, which promotes the opening of the channel and allows the ON-bipolar cells to transmit the light signal.

"It really takes a combined effort of the two RGS proteins to help the light overcome the barrier for propagating the excitation that makes our dim vision possible," Dr. Martemyanov said.

In a second study, published in the Journal of Cell Biology, Dr. Martemyanov’s team unraveled another key aspect of the proteins’ regulatory response, identifying a previously unknown pair of orphan G protein-coupled receptors (GPCRs) that interact with the RGS proteins and dictate their biological function.

GPCRs are a large family of proteins that sit in the cell membrane and sense various molecules outside the cell, including odors, hormones and light. After binding to these molecules, GPCRs trigger the appropriate response in the cell. But for many GPCRs, the activating molecules have not been identified. These are termed "orphan" receptors.

Dr. Martemyanov's study found that two orphan GPCRs recruit RGS proteins and thus serve as brakes for conventional GPCR signaling, rather than play an active signaling role.

In the case of retinal ON-bipolar cells, one of the newly identified GPCRs is required in order to correctly localize the two RGS proteins. Night blindness, in fact, may be caused by their mistargeting in patients with mutations in that gene.

"We are really in the very beginning of unraveling this new biology…The hope is that better understanding of these new molecules will lead to the design of better treatments for addictive disorders, pain and blindness," Dr. Martemyanov said.

Source: Scripps Research Institute