UC Santa Cruz

The retina is a thin layer of neural tissue that lines the back of the eye and transforms the visual scene into an electrical signal that is sent to the brain via the optic nerve. The synapse between photoreceptors, the light sensitive neurons, and bipolar cells is the first connection in the retinal circuitry. Loss of photoreceptors during retinal degeneration results in permanent visual loss. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of bipolar cells to establish new functional synapses with photoreceptors is poorly understood. In my work, I investigate if deafferented bipolar cells, i.e. the ones that lost photoreceptors, in the adult mammalian retina can rewire with new photoreceptors. I use focal laser photocoagulation to selectively ablate a small patch of photoreceptors while leaving the rest of the retinal neurons intact. I use electrophysiology recordings of retinal response to visual stimuli to show that the neighboring healthy photoreceptors shift into the ablation zone, thus returning visual sensitivity to the previously deafferented bipolar cells. Furthermore, I use immunohistochemistry to determine if the new synapses of the deafferented bipolar cells are selective for appropriate pre-synaptic partners and investigate the structural mechanisms bipolar cells use to find new partners. I find that deafferented bipolar cells are capable of rewiring correctly with new photoreceptors, but different bipolar cell types use different rewiring strategies. I also find that the new synapses may not be as selective as those in the healthy retina. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. However, the diversity of responses to deafferentation between bipolar cell types shows that different parallel pathways have access to different plasticity mechanisms, suggesting that they will respond to photoreceptor reintroduction therapies differently. Improving our understanding of the plasticity within the adult retina is important for the success of future vision restoration therapies.