New Tools for Leveraging Regenerative Medicine to Restore Sight in Glaucoma
Thomas Johnson III is on a mission. Johnson, a clinician-scientist and the Allan and Shelly Holt Rising Professor of Ophthalmology at Wilmer Eye Institute, Johns Hopkins Medicine, specializes in treating people with glaucoma. He laments that while he can provide therapy to help people with glaucoma maintain the vision they have, patients often arrive to his care already having lost significant vision.
At present, there is no treatment that will restore vision after it has been lost to glaucoma, but he aims to change that, with the help of a National Glaucoma Research Award from the BrightFocus Foundation. We spoke with Johnson to learn more about his research and what he hopes to accomplish with the generous support of the foundation.
What is the goal of your research?
Vision restoration in glaucoma will require the replacement of optic nerve neurons called retinal ganglion cells (RGCs), which die as a consequence of glaucoma. RGCs are the “relay neurons” of the eye, meaning that they directly communicate visual information from the eye to the brain, so connecting donor RGCs to the recipient retina is essential. My first goal is to develop an innovative “reporter” tool, wherein donor RGCs will glow blue only after making functional connections to the host retina. The second goal is to develop a multicolor adaptive optics microscope capable of monitoring donor RGC engraftment into the host retina in living eyes. My colleague Ji Yi is a collaborator on this part of the project.
With these sophisticated microscopy instruments and human stem cells genetically engineered to contain a fluorescent reporter, we will be able to directly visualize neuronal regeneration in real time.
What is unique or innovative about your approach?
Unlike traditional methods of studying connectivity between neurons, this approach will allow the study of many individual cells simultaneously, and will label connected cells automatically and in real-time so they can be tracked through imaging. It can be applied to multiple different experimental model systems and species, and it will enable downstream studies of engrafted neurons and comparison to non-engrafted neurons.
What are the foreseeable benefits to the general public and your research field?
This work will help bring RGC transplantation closer to human clinical trial for vision restoration in glaucoma and other optic neuropathies. We will broadly share the tools developed through this study to enable investigators to study synaptic connectivity of transplanted neurons in the retina (and in other parts of the central nervous system, like the brain and spinal cord) with high-throughput, single-cell resolution. We hope such work will enable clinical translation of neuronal transplantation to achieve functional recovery in multiple neurodegenerative diseases.
What motivated you to pursue this line of research?
At least once a month, I meet a patient for the first time and have the difficult job of providing a diagnosis of end-stage glaucoma. Dubbed the “sneak thief of sight,” glaucoma can be insidious — painless and so slow that some people do not notice vision loss until they have only a central 2-degree island of vision remaining. Other patients come to me with the total inability to even detect light in one or both eyes. While I can provide therapy that will help such patients maintain the vision they have, at present neither I nor anyone in the world can offer a treatment that will restore vision after it has been lost to glaucoma. My driving motivation is, one day, to be able to improve the lives of my patients with the most severe cases of glaucoma — to tell them that I am not only their doctor, but their partner on the road to vision restoration. And I wish that for all glaucoma doctors and patients worldwide.
In addition to receiving funding from the BrightFocus Foundation for his proposal titled “In vivo adaptive optics ophthalmoscopy to characterize functional retinal integration of transplanted RGCs using a novel transgenic reporter paradigm,” Johnson is the recipient of the Dr. Douglas H. Johnson Award, presented annually to the top-rated proposal in the National Glaucoma Research program.