Study: Retinal photoreceptors use dual pathways to tell brain ‘I’ve seen the light!’


A team of neuroscientists at Johns Hopkins show how specialized cells signal the presence of light simultaneously in two distinct ways.

Burst of yellow light on a black background (Image credit: AdobeStock/sanee)

(Image credit: AdobeStock/sanee)

A team of neuroscientists at Johns Hopkins Medicine have used mammalian retinal cells to show that, unlike most light-sensing cells (photoreceptors) in the retina, one special type uses two different pathways at the same time to transmit electrical “vision” signals to the brain.

The researchers also found that those photoreceptors may have ancient origins on the evolutionary scale.

This and other findings, published December 18, 2023, in Proceedings of the National Academy of Sciences,1brought into focuson a decades-long mystery about how such cells work, the researchers say.

According to a Johns Hopkins Medicine news release,2 the research was co-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 news release noted that King’s previous work led to advances in understanding how light-sensing cells in the mammalian eye transmit signals to the brain, findings that may eventually help scientists learn why people without sight can still sense light.

In animals, including humans, photoreceptors (light-sensing cells) called rods and cones are located in the retina, a tissue layer at the back of the eye that responds to light. The rods and cones analyze visual signals that are transmitted via electrical signals to the brain, which interprets what is “seen.”

The researchers pointed out in their research that another type of photoreceptor in the retina, called intrinsically-photosensitive retinal ganglion cells (ipRGCs), use long protrusions (axons) that form the optic nerve to convey visual signals from rods and cones. The ipRGCs also perform other functions, such as setting the body’s light-driven circadian rhythms and distinguishing contrast and color.1

According to the news release, it has been known that photoreceptors in animals detect light by using a signaling pathway named for the cell’s origin. Photoreceptors of “microvillous” origin, similar to those in the fruit fly eye, use the enzyme phospholipase C to signal light detection — whereas, photoreceptors of ciliary origin, such as those in our rods and cones, use a cyclic-nucleotide pathway. The photoreceptors, to signal light detection, rely upon either the microvillous or ciliary pathway, not both. However, in experiments to further understand how ipRGCs work, Yau’s team found that ipRGCs use both pathways at the same time.

Moreover, the researchers found this by exposing ipRGCs to brief pulses of bright light. Under those conditions, the microvillous signaling pathway produces faster electrical responses and precedes, with some overlap, a slower response by the ciliary pathway.1

Johns Hopkins Medicine noted that Yau’s team found that all 6 subtypes of ipRGCs use both microvillous and ciliary signaling mechanisms — although at different percentages — at the same time.

According to the news release, the Johns Hopkins team also found that while most photoreceptors using the ciliary signaling pathway use a particular cyclic nucleotide, cGMP, as the signaling messenger, ipRGCs use another, cAMP, which is similar to jellyfish, an animal much older on the evolutionary scale. This suggests that ipRGCs may have an ancient origin.2

Other Johns Hopkins researchers who contributed to this study are Lujing Chen and Zheng Jiang.

The news release also noted the study was funded by a grant from the National Institutes of Health (R01 EY014596) and a Beckman-Argyros Award in Vision Research.

1. Li G, Chen L, Jiang Z, Yau K. Coexistence within one cell of microvillous and ciliary phototransductions across M1- through M6-IpRGCs. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(52). doi:
2. Retinal Photoreceptors Use Dual Pathways to Tell Brain “I’ve Seen the Light!” Accessed February 6, 2024.
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