SCHEIE VISION | ANNUAL REPORT 2020
NEW METHOD OF GENERATING RETINAL GANGLION CELLS: STEP TOWARDS TARGETED GLAUCOMA THERAPY By Alexandra Brodin
Dr. Chavali in his lab, sequencing DNA obtained from patient stem cells to identify pathogenic mutations that make individuals susceptible to glaucoma.
Venkata R. M. Chavali, PhD, Assistant Professor of Ophthalmology at the University of Pennsylvania (UPenn), recently led a study to develop a promising new methodology for differentiating stem cells into retinal ganglion cells (RGCs) in vitro. This methodology has the potential to lead to more targeted treatments for glaucoma, the leading cause of irreversible blindness worldwide.
A NEW VISION FOR TREATING GLAUCOMA Primary open-angle glaucoma (POAG), the most common form of the disease, is characterized by chronic, progressive degeneration of the optic nerve, a cord-like structure responsible for carrying neural signals from the eyes to the brain. Damage to the optic nerve is caused by the death of retinal ganglion cells (RGCs), which are neurons located in the retina. The axons of RGCs collectively form the optic nerve. Current therapeutic strategies for glaucoma focus on management of intraocular pressure (IOP) to slow disease progression. However, even if diagnosed in early stages,
approximately 30% of patients continue to worsen despite IOP-lowering treatments. This suggests that more research is needed on additional underlying disease mechanisms independent of elevated IOP, which, once understood, could provide further therapeutic targets for glaucoma. Because human RGCs do not regenerate naturally after they deteriorate, the idea to restore or replace damaged RGCs is very attractive as a potential therapy. Stem cells provide investigators with the opportunity to generate new, viable RGCs. These RGCs can then be used to study the various factors that cause these cells to deteriorate in vitro and in mouse models. In recent years, vision scientists have found that RGCs can be generated using induced pluripotent stem cells (iPSCs), which are somatic cells that have been reprogrammed to an embryonic-like state. Researchers can guide iPSCs toward any type of cell lineage that may be required for experimental and therapeutic purposes, including the RGC lineage. The differentiation of iPSCs toward the RGC lineage allows researchers to study how to slow RGC death
