Florida scientists make night blindness breakthrough

Florida scientists make night blindness breakthrough

Recent reports by scientists in the US have shed light on an important function of the eyes and how they work, which could have a significant impact on future research into treatments for eye conditions.

Two related studies carried out by scientists from the Florida campus of The Scripps Research Institute have identified several proteins that help regulate cells' response to light.

In addition, it has helped them to better understand night blindness, a rare disease that abolishes the ability to see in dim light.

The studies were published in the journals Proceedings of the National Academy of Sciences (PNAS) and The Journal of Cell Biology, where the experts showed that a family of proteins known as Regulator of G protein Signalling (RGS) proteins play an essential role in vision in a dim-light environment.

Kirill Martemyanov, a Scripps Research associate professor who led the research, explained that scientists were looking at the fundamental mechanisms that shape people's light sensation.

"In the process, we discovered a pair of molecules that are indispensible for our vision and possibly play critical roles in the brain," he added.

The first study found that a pair of regulator proteins, known as RGS7 and RGS11 are present specifically in the main relay neurons of the retina called the ON-bipolar cells, which themselves provide an essential link between the retinal light detectors - photoreceptors and the neurons that send visual information to the brain.

Professor Martemyanov explained that stimulation with light excites these neurons by opening the channel that is normally kept shut by the G proteins in the dark.

"RGS7 and RGS11 facilitate the G protein inactivation, thus promoting the opening of the channel and allowing the ON-bipolar cells to transmit the light signal," he explained.

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

In the second study, the experts unravelled another key aspect of the RGS7/RGS11 regulatory response when identifying a previously unknown pair of orphan G protein-coupled receptors (GPCRs) that interact with these RGS proteins and dictate their biological function.

GPCRs are a large family of more than 700 proteins, which sit in the cell membrane and sense various molecules outside the cell, including odours, hormones, neurotransmitters, and light.

After binding these molecules, GPCRs trigger the appropriate response inside the cell, but in the case of many GPCRs the activating molecules have not yet been identified and these are called “orphan” receptors.

The experts found that two orphan GPCRs - GPR158 and GPR179 - recruit RGS proteins and thus help serve as brakes for the conventional GPCR signalling, rather than play an active signalling role.

In the case of retinal ON-bipolar cells, GPR179 is required for the correct localisation of RGS7 and RGS11.

According to the experts, their mistargeting in animal models lacking GPR179 or human patients with mutations in the GPR179 gene may account for their night blindness.

Professor Martemyanov said it is intriguing that, in the brain GPR158 appears to play a similar role in localising RGS proteins, but instead of contributing to vision, it helps RGS proteins regulate the m-opioid receptor, a GPCRs that mediates pleasurable and painkilling effects of opioids.

"We are really in the very beginning of unravelling this new biology and understanding the role of discovered orphan GPR158/179 in regulation of neurotransmitter signalling in the brain and retina," the expert explained.

"The hope is that better understanding of these new molecules will lead to the design of better treatments for addictive disorders, pain, and blindness."ADNFCR-1853-ID-801385970-ADNFCR

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