Using adaptive optics, researchers at the University of Rochester (UR) identified some of the rare, non-cardinal retinal ganglion cells (RGCs) in the fovea of the eye. The UR team’s discovery could improve scientific understanding of how humans perceive color and eventually lead to new solutions for treating vision loss. RGCs provide the only source of visual information to the brain, and thus make up the building blocks for downstream visual processing. Accordingly, a complete account of how RGCs compare the cone photoreceptors is critical to a comprehensive knowledge of color vision. The retina has three types of cone photoreceptors that detect color. These cone receptors are sensitive to short, medium, and long wavelengths of light, respectively. The cones send input about color to the RGCs, and the RGCs transmit the input to the central nervous system. The input sent from the cones to the most common RGCs establish "cardinal directions" in color space that can explain color direction, but not color appearance. Scientists theorize that, while most RGCs follow the cardinal directions, they also may work in tandem with small numbers of non-cardinal RGCs to create more complex color perceptions. Color perception is one of the few areas where engineering has outpaced basic science, according to postdoctoral researcher Sara Patterson, who led the study. “Humans have more than 20 ganglion cells and our models of human vision are only based on three,” she said. “There’s so much going on in the retina that we don’t know about.” The team leveraged adaptive optics, a method that uses a deformable mirror to overcome light distortion. The technique, first developed for use in astronomy, has been used at UR to study the human eye since the 1990s. The researchers created a camera that compensates for distortion caused by natural aberrations in the eye to produce a clear image of individual photoreceptor cells. “The optics of the eye’s lens are imperfect and really reduce the amount of resolution you can get with an ophthalmoscope,” Patterson said. “Adaptive optics detects and corrects for these aberrations and gives us a crystal-clear look into the eye. This gives us unprecedented access to the retinal ganglion cells, which are the sole source of visual information to the brain.” As the brain’s only source of visual information, RGCs play an essential role in how neural circuits process color perception downstream. The team performed calcium imaging to noninvasively measure foveal RGC light responses in the living macaque eye. Using this technique, the team confirmed the presence of neurons with non-cardinal cone-opponency and demonstrated that cone-opponent signals in the retinal output are more diverse than traditionally thought. The foveal RGCs with non-cardinal cone opponency matched the cone inputs to red, green, blue, and yellow. While this correlation does not validate any connection between non-cardinal RGCs and how color is perceived, it could open new directions to study neural processing of color and help fill gaps in existing theories about color perception. “We don’t really know anything for certain yet about these cells other than that they exist,” Patterson said. “There’s so much more that we have to learn about how their response properties operate, but they’re a compelling option as a missing link in how our retina processes color.” With a better understanding of how non-cardinal RGCs contribute to color perception, researchers could, for example, potentially develop retinal prosthetics that would drive ganglion cells according to the cells’ functional roles. The research was published in the Journal of Neuroscience (www.doi.org/10.1523/JNEUROSCI.1738-23.2024).