Dual Signaling Pathways in Retinal Photoreceptors Discovered by Johns Hopkins Research: Potential Paradigm Shift in Eye Disease Treatment

New Insights into Retinal Cell Functioning

Some retinal photoreceptors use two signaling pathways to tell the brain they have sensed light, as revealed by a team of neuroscientists from Johns Hopkins University. A particular type of specialized cell signals the presence of light in two distinct ways simultaneously. These experimental works, published in the Proceedings of the National Academy of Sciences of the United States (PNAS), shed scientific light on a decades-old mystery about the functioning of these retinal cells.



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The research team worked on mammalian retinal cells and observed that, unlike most photosensitive cells (photoreceptors) in the retina, a particular type uses two distinct pathways simultaneously to transmit vision electrical signals to the brain. The studies also reveal that these photoreceptors, according to the researchers, could have more ancient origins in the course of evolution.

Previous research by the same team, led by King-Wai Yau, professor of neuroscience, and researcher Guang Li, at Johns Hopkins University, had already allowed a better understanding of how the photosensitive cells of the eye transmit signals to the brain. This also helped to better understand why blind people can still perceive light.

Mechanisms of Light Detection in Photoreceptors

How it works: in animals and humans, light-sensitive cells, the photoreceptors called rods and cones, located in the retina and in a layer of tissue at the back of the eye, react to light. Rods and cones analyze visual signals transmitted through electrical signals to the brain, which then interprets these signals. Another type of retinal photoreceptor called intrinsically photosensitive retinal ganglion cells (ipRGC), already known to be involved in non-visual functions including circadian rhythm, use long extensions, the axons, -which form the optic nerve- to transmit visual signals from the rods and cones. These ipRGCs in fact also fulfill other functions, such as setting the body’s light-based circadian rhythms and distinguishing contrast and color.

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Dual Signaling Pathways in ipRGCs

Two-way photoreceptors: photoreceptors like those in the eye of the fruit fly use the enzyme phospholipase C to signal light detection, while other ciliary-origin photoreceptors, like those of rods and cones, use another signaling pathway. To signal light detection, most photoreceptors use one of these pathways, however, the ipRGCs use both pathways at the same time.

When researchers expose ipRGCs to brief pulses of intense light, the first signaling pathway produces faster electrical responses and precedes, with some overlap, a slower response from the second pathway. These particular photoreceptors, the ipRGCs, thus simultaneously use both signaling mechanisms in different percentages.

If most photoreceptors that use the second signaling pathway use a particular cyclic nucleotide, cGMP, as a signaling messenger, the ipRGCs use another, cAMP, also found in jellyfish, a much older animal on the evolutionary scale. This suggests that ipRGCs could have an older origin in our evolution.

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Final Thoughts

This research could influence the development of eye treatments and implants. By understanding these dual pathways in retinal cells, there’s potential for improved retinal implants that more closely mimic natural eye functions. Additionally, this knowledge might lead to more targeted treatments for eye conditions like macular degeneration and retinitis pigmentosa. Essentially, this advances our approach to eye health, potentially offering more effective solutions for various vision impairments.


Li, G., Chen, L., Jiang, Z., & Yau, K.-W. (2023). 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, 120(52), e2315282120. https://doi.org/10.1073/pnas.2315282120



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