MCW Vision Scientists Publish Two New Papers
Dr. Joseph Carroll, co-Director, Dennis P. Han, MD Advanced Ocular Imaging Program and Richard O. Schultz, MD / Ruth Works Professor in Ophthalmology at the Medical College of Wisconsin is one of the authors on a recent paper published in JNeurosci, The Journal of Neuroscience, titled “Optoretinography in R9AP-Bradyopsia Reveals an Essential Role of G-Protein Activation and Deactivation in the Human Cone Elongation Response.”
This study uses optoretinography to watch how individual cone photoreceptors in the living human eye respond to a flash of light, in real time and without any invasive procedure. The researchers studied patients with a rare condition called bradyopsia, caused by mutations in the RGS9 or R9AP genes, which slow down the "shut-off" step of the visual signaling cascade inside photoreceptors (the same G-protein pathway phones use as an analogy for on/off switches in vision). By comparing how quickly cones elongate and recover in these patients versus people with normal vision, the team showed that this shut-off machinery is essential for the eye's light response to reset properly. The work establishes optoretinography as a non-invasive way to directly probe G-protein signaling in the human retina – a tool that could help diagnose retinal diseases earlier and track whether future gene or drug therapies are actually working at the molecular level.
MCW graduate students Darby Bennett and Robert Newland, published an article with Matthew Veldman, PhD, and Joel Miesfeld, PhD, in Investigative Ophthalmology & Visual Science, an ARVO journal, titled “Lineage Tracing Reveals atoh7-Positive and Negative Retinal Ganglion Cell Populations in the Zebrafish Retina.”
In this study, researchers study retinal ganglion cells, the neurons lost in glaucoma that carry visual signals from eye to brain and their dependence on a gene called atoh7 during development, but not all of them actually descend from cells that once switched it on. Using zebrafish, researchers built a genetic tracing system to permanently mark cells descended from atoh7-expressing ancestors, revealing that about 79% of retinal ganglion cells trace back to this lineage – higher than the roughly 55% seen in mice – while nearly every other retinal cell type carries some atoh7 ancestry as well. The findings give scientists a precise new tool for understanding why some of these critical neurons need atoh7 to survive and others don't, a question with direct relevance to protecting vision in diseases like glaucoma.