Retinitis Pigmentosa (RP) is a genetic blindness disease that afflicts millions worldwide. Although patients with this disease are born with the mutation that causes it, the age of onset is often during childhood or adolescence. Usually, a typical patient will go to the doctor’s office because of progressive night vision problems, at which point, the underlying causal mutation may be identified by genetic testing. While night vision impairment is troublesome, it is not life-altering. Unfortunately, over the next years to decades, daylight color vision progressively deteriorates, and some patients completely lose their vision. Recent advancements in gene therapy have successfully corrected one of the underlying mutations, leading to the preservation of vision in patients suffering from RP. However, over 65 causal genes have been identified that cause RP, and developing a gene therapy for each gene is not feasible. Regardless of the gene mutation, the disease ultimately converges upon progressive daylight color vision loss, which is due to the death of cone photoreceptors, which are the cells in the back of the eye that allow us to capture daylight color vision. The long-term goal of this project is to promote cone photoreceptor survival in this disease in order to prolong healthy daylight color vision for all patients suffering from RP. In our previous work, we identified a new set of genes that, when activated, promotes cone photoreceptor survival in a mouse model of RP. In this grant, we are proposing three projects to take this study closer to the clinic. One, we will test a new delivery method to activate these genes called AAV, which is the current delivery method of choice for gene therapy. Second, we will reactivate these surviving cones by using a bacterial ion pump that reacts to light. Third, we will elucidate the mechanism by which RA signaling promotes cone survival by dissecting the genes downstream of the signaling pathway.  In sum, completing these projects will lead us one step closer to prolonging healthy vision for all patients suffering from RP.