Shedding light on migraines: Signals from the eye make people with migraine more sensitive to light
or technically,
Selective amplification of ipRGC signals accounts for interictal photophobia in migraine
[See Original Abstract on Pubmed]
Authors of the study: Harrison McAdams, Eric A Kaiser, Aleksandra Igdalova, Edda B Haggerty, Brett Cucchiara, David H Brainard, Geoffrey K Aguirre
Have you ever stepped outside and had to squint or shield your eyes from the sun? Bright light can be uncomfortable for anyone, but it can be especially painful to those who experience migraines. While headaches are often associated with migraines, another common symptom is photophobia, or sensitivity to light. Harrison McAdams, a neuroscience student in Dr. Geoffrey Aguirre‘s lab
at Penn, wanted to find out what part of the eye or brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. might be responsible for the symptom of photophobia in migraines.
In order to discover how photophobia might arise, we need to understand how our eyes allow us to see our surroundings. The first step in vision is when light hits the retina, a sheet of cells that covers the back of the eye. The retina is made of three layers of neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles with specific functions. Some of these neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles can detect light: these are the rods and cones, and they become excited by photons, the particles that make up light. Rods work in dim light, while cones work in bright light and can sense red, green, or blue light. This is how we’re able to see in color! Rods and cones talk to other neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the retina like RGCs (retinal ganglion cells), which then send signals out of the eye and to many different areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
In order to discover how photophobia might arise, we need to understand how our eyes allow us to see our surroundings. The first step in vision is when light hits the retina, a sheet of cells that covers the back of the eye. The retina is made of three layers of neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles with specific functions. Some of these neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles can detect light: these are the rods and cones, and they become excited by photons, the particles that make up light. Rods work in dim light, while cones work in bright light and can sense red, green, or blue light. This is how we’re able to see in color! Rods and cones talk to other neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the retina like RGCs (retinal ganglion cells), which then send signals out of the eye and to many different areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
Most RGCs just listen to the rods and cones that talk to them; however, there are special RGCs that are “intrinsically photosensitive” (ipRGCs), which means they can detect light just like rods and cones do. These ipRGCs actually don’t help you see images. Instead, they are responsible for your sense of a day/night cycle and for helping your pupils adjust to the light or dark. There is also evidence that ipRGCs connect to the thalamus, an area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. which can sense pain. Harrison thought this connection could explain why light can be especially painful to people with migraine.
60 people participated in this study: 40 experienced photophobia from migraines and 20 did not have migraines for comparison. Pulses of different colored light were flashed in one eye to either activate the cones, the ipRGCs, or both. They rated how painful each flash of light was on a scale from 0 to 10, 10 being the most painful. People with photophobia tended to rate the “cone” light as more painful compared to those without, and their rating increased as the light got brighter. Since we know that they’re sensitive to bright light and that cones work in bright light, this makes sense. Interestingly, they also gave higher pain ratings to light which only activated the ipRGCs.
From this test, Harrison knew that ipRGC activity could cause pain. After recording pupil size while the light was flashing, he found no difference in people with or without migraine. This means that not all ipRGC functions are affected: It’s a specific strengthening of the signal from the retina to the pain-sensing area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
Why would our eyes be wired like this? Just like touching a hot stove can damage your hand, staring at the sun or shining a flashlight in your eyes can damage your retinas. And once those neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are gone, they’re gone for good--so take care of them! Although this signal can be helpful, warning us that what we’re doing is harmful, it seems like when the signal becomes too strong, people can develop migraines. Identifying the root of the problem is the first step in developing treatments to help people who live with this condition.
60 people participated in this study: 40 experienced photophobia from migraines and 20 did not have migraines for comparison. Pulses of different colored light were flashed in one eye to either activate the cones, the ipRGCs, or both. They rated how painful each flash of light was on a scale from 0 to 10, 10 being the most painful. People with photophobia tended to rate the “cone” light as more painful compared to those without, and their rating increased as the light got brighter. Since we know that they’re sensitive to bright light and that cones work in bright light, this makes sense. Interestingly, they also gave higher pain ratings to light which only activated the ipRGCs.
From this test, Harrison knew that ipRGC activity could cause pain. After recording pupil size while the light was flashing, he found no difference in people with or without migraine. This means that not all ipRGC functions are affected: It’s a specific strengthening of the signal from the retina to the pain-sensing area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
Why would our eyes be wired like this? Just like touching a hot stove can damage your hand, staring at the sun or shining a flashlight in your eyes can damage your retinas. And once those neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are gone, they’re gone for good--so take care of them! Although this signal can be helpful, warning us that what we’re doing is harmful, it seems like when the signal becomes too strong, people can develop migraines. Identifying the root of the problem is the first step in developing treatments to help people who live with this condition.
About the brief writer: Sierra Foshe
Sierra is a PhD student in Josh Dunaief's lab. She is interested in the mechanisms of retinal inflammation and degeneration.