Researchers at the Herbert Wertheim School of Optometry & Vision Science have uncovered rare neurons in the eye crucial for maintaining a sharp, steady visual image of the world. These findings not only impact our understanding of the human retina but also offer potential insights into the pathology of eye movement disorders.
The groundbreaking discovery reveals, for the first time, the presence of retinal neurons responsible for gaze stabilization in other mammals, in primates, including humans. These neurons, termed retinal ganglion cells, transmit visual signals from the eye to the brain. In humans, there exist approximately 20 distinct retinal ganglion cell types, each responding to specific visual scene features like form, color, and motion.
Among these cell types, the researchers identified a highly specialized one known as direction-selective ganglion cells (DSGCs). These cells respond to motion in the visual field by increasing activity in their "preferred" direction while exhibiting minimal activity in the opposite direction. The collective responses from these neurons convey information to the gaze stabilization system, indicating the direction of movement in the visual scene.
“This cell type in particular—the direction-selective ganglion cell—had not been discovered previously in primate despite concerted effort, leading the field to conclude it must not be there,” said Marla Feller, PhD, a distinguished professor at UC Berkeley and an elected member of the National Academy of Sciences. Dr. Feller is an expert in retinal circuit development and function.
Direction-selective ganglion cells (DSGCs) were initially identified in the rabbit retina in 1964 by another faculty member of Berkeley Optometry, Horace Barlow, and his colleagues. Despite this discovery, the absence of evidence for DSGCs in higher species over subsequent decades led scientists to hypothesize that primate direction selectivity was computed in the brain. However, with the emergence of new evidence indicating a potential connection between abnormal activity of DSGCs and certain human gaze stabilization disorders, Puthussery's lab reinvigorated their efforts to locate these cells.
“That was a tipping point. We thought DSGCs had to be there, but that they made up a very low percentage of retinal ganglion cells. Our challenge was to work out how to find the needle in the haystack,” said Dr. Puthussery.
To address this challenge, the researchers employed a comprehensive strategy. Initially, they utilized data from cutting-edge genetic tools to identify retinal neurons sharing molecular characteristics with DSGCs found in other animals. Subsequently, these neurons were labeled with fluorescent markers to confirm their anticipated anatomical features. Finally, the team developed a specialized imaging system to monitor the activity of numerous retinal ganglion cells, demonstrating that the fluorescently tagged cells exhibited selective responses to images moving in specific directions. This integration of molecular, anatomical, and functional evidence conclusively identified the elusive DSGCs.
“The Puthussery Lab was successful where others failed because of their novel approach,” said Dr. Marla Feller. She continued, “I also cannot overstate the high quality of the data, which is critical for such a breakthrough finding.”
These findings will enhance researchers' understanding of how retinal mechanisms contribute to gaze stabilization in both the normal visual system and in disorders that result in unstable gaze. One such disorder is nystagmus, characterized by repetitive, uncontrolled eye movements that can lead to unsteady and blurry vision. Nystagmus may occur independently or accompany other eye conditions, such as albinism and specific inherited retinal diseases. While various forms of nystagmus are typically attributed to issues in the brain or inner ear, the outcomes of this study suggest that certain types of nystagmus might stem from abnormal activity of direction-selective ganglion cells (DSGCs) in the retina.
Overall, these findings vividly illustrate that even a rare retinal ganglion cell type can significantly influence our overall visual perception. The methodology employed in this study can now be extended to elucidate the functions of other types of human ganglion cells with unknown roles. This marks a crucial advancement in developing more precise tests for detecting blinding diseases characterized by ganglion cell degeneration, such as glaucoma—an ailment affecting 80 million people globally and standing as the primary cause of irreversible blindness. To illustrate, if direction-selective ganglion cells suffer early damage in glaucoma, alterations in eye movements could potentially serve as an objective biomarker for detecting early-stage damage.