Understanding the degenerate retina's response to electrical stimulation : an in vitro approach

[摘要] Retinitis pigmentosa (RP) and age‐related macular degeneration (AMD) are two common outer retinal diseases for which there are currently no cures. These degenerative diseases initiate the death of photoreceptor cells and can ultimately lead to complete blindness. Despite the loss of these cells, however, much of the inner retina remains intact providing a potential means for signal transmission to higher visual centers. Various approaches to elicit visual percepts through retinal stimulation have demonstrated the feasibility of engaging the remaining retina to convey visual information to the brain. ❧ One strategy for inducing activity in residual retinal cells is to stimulate the retinal ganglion ganglion cells (RGCs) electrically. RGCs receive information from inner retinal cells and send visual information, encoded in trains of action potentials, along their axons to higher visual centers. Significant rewiring and remodeling as well as individual structural changes in inner retinal cells have been observed in human retina as well as various animal models of degeneration. Therefore, direct stimulation of RGCs can bypass the anomalous inner retina circuitry. However, RGC firing patterns, both spatial and temporal, are critical to vision. To be able to best replicate natural vision, bioelectronic‐based vision restoration therapy must have exquisite control of RGC firing, which requires a thorough understanding of how electrical stimulation elicits responses from RGCs. ❧ The physiological behavior of RGCs in normal and degenerate mice was measured using whole‐cell patch clamp recordings. Results presented in this thesis demonstrate that thresholds in degenerate ganglion cells are significantly elevated and highly variable compared to normal controls, despite having comparable chronaxie values and response latencies. Degenerate RGCs display increases in baseline spontaneous firing not commonly seen in wildtype cells. Furthermore, there is a significant correlation between higher spontaneous rate and reduced stimulation thresholds in degenerate cells; spontaneous activity is not correlated with thresholds in normal RGCs. These findings suggest that the physiology of RGCs is altered as degeneration progresses and may be due to intrinsic changes in ganglion cells as well as synaptic contributions from bipolar and amacrine cells. ❧ The aim of the work presented in this thesis is to assess physiological properties of retinal ganglion cells in a model of retinal degeneration, and to determine how degenerate RGC physiology influences the response to electrical stimulation. This study is part of an ongoing effort toward development of an epiretinal prosthesis for sight restoration.

[发布机构] University of Southern California . Libraries