CLFB143 Analogs to Treat Glaucoma

Project Summary Glaucoma is the leading cause of irreversible blindness worldwide. In glaucoma, retinal ganglion cells (RGCs), the projection neurons that transmit vision from the retina to the brain, are injured and die, partially as a result of increasedintraocular pressure (IOP). Current therapies (laser, surgery and eye drops) all act by lowering IOP. Unfortunately, lowering IOP can produce undesirable side effects and/or be difficult to achieve. Moreover, in some patients, RGC loss continues despite significant IOP reduction. Lacking are neuroprotective agents that directly interfere with the cell death process in RGCs. The development of safe and efficacious neuroprotective agents would improve glaucoma therapy by complementing the currently available IOP treatment options. In order to identify such compounds, the Zack group at Johns Hopkins developed a high- content, high-throughput small molecule screen using RGCs. This takes advantage of the ability to isolate and culture primary murine RGCs and