Coexistence of Two Signaling Pathways in Light-Sensing Cells in the Retina

Sunday - March 3 2024, 13:14 UTC - 8 months ago

Neuroscientists at Johns Hopkins have discovered that a type of light-sensing cell in the retina uses both a microvillous and ciliary signaling pathway at the same time to transmit visual signals to the brain. This finding sheds light on a decades-long mystery and suggests that these cells may have an ancient origin. ipRGCs, which have multiple functions beyond vision, use a different signaling molecule compared to most photoreceptors, similar to jellyfish.

Working with mammalian retinal cells, neuroscientists at Johns Hopkins Medicine have shown that a special type of light-sensing cell in the retina uses two different pathways at the same time to transmit visual signals to the brain. This finding sheds light on a decades-long mystery and has implications for our understanding of the evolution of vision.

In animals, including humans, photoreceptors called rods and cones are responsible for detecting and analyzing visual signals. These cells are located in the retina, a tissue layer at the back of the eye. In addition to rods and cones, the retina also contains a type of photoreceptor called intrinsically-photosensitive retinal ganglion cells (ipRGCs). These cells serve multiple functions in addition to vision, such as setting the body's circadian rhythms and distinguishing contrast and color.

Led by King-Wai Yau, Ph.D., professor in the Department of Neuroscience at the Johns Hopkins University School of Medicine, and postdoctoral fellow Guang Li, the research team investigated how ipRGCs transmit visual signals to the brain. Their previous work had already advanced our understanding of how light-sensing cells in the mammalian eye work and may eventually lead to insights into why people without sight can still sense light.

Unlike most photoreceptors which use either a microvillous or ciliary signaling pathway to transmit light detection signals, Yau's team found that ipRGCs use both pathways simultaneously. This was discovered through experiments in which ipRGCs were exposed to brief pulses of bright light. The researchers found that the microvillous pathway produced a faster electrical response, which then overlapped with a slower response from the ciliary pathway.

Further investigation revealed that all six subtypes of ipRGCs use both the microvillous and ciliary signaling mechanism, although at different percentages. This suggests that using both pathways at the same time may be a common feature among ipRGCs.

Interestingly, while most photoreceptors that use the ciliary pathway as their main signaling mechanism use a signaling molecule called cGMP, ipRGCs use a different molecule called cAMP. This molecule is also used by jellyfish, an animal with an ancient evolutionary lineage. This discovery led the researchers to speculate that ipRGCs may have an ancient origin on the evolutionary scale.

In conclusion, the findings of this research, recently published in PNAS, have shed light on a long-standing mystery surrounding the signaling mechanisms of ipRGCs. By using both microvillus and ciliary signaling pathways simultaneously, these cells may have an important role in the evolution of visual systems.