Title: Targeting Muller Cells to Treat Optic Nerve Injury Principal Investigator: Sherry L. Ball, PhD Objectives A substantial proportion of returning veterans diagnosed with traumatic brain injuries (TBI) also exhibit visual deficits. The VA Polytrauma Rehabilitation Center in Palo Alto, CA, has reported that approximately 70% of their traumatic brain injury patients experience visual deficits. Given the large proportion of returning soldiers from Operation Enduring Freedom and Operation Iraqi Freedom with traumatic brain injury it is clear that studies investigating how ocular trauma affect retinal and visual function are urgently needed. Our goal is to identify the underlying signals triggering degenerative processes in the retina. It is well established that both glial and neuronal cells in the retina respond to ocular trauma. Recent studies suggest that neuronal degeneration is exacerbated by glial cell reactivity. We hypothesize that alterations in glial cell function contribute to vision losses and that the modulation of glial cell reactivity will minimize retinal degeneration and thus vision loss. Research Plan We will test the hypothesis that a) loss of vision following TBI involves reactive events triggered by retinal M?ller cells and b) that retinal degeneration and vision loss can be prevented or slowed by treatment with anti-inflammatory agents which target M?ller cells. Methodology Electroretinography (ERG) will be used to noninvasively follow retinal function and injury responses in the retina using no b-wave (nob) and wild type (WT) mice following optic nerve crush. The nob mouse is a naturally occurring mutant mouse in which M?ller cell function as represented in the ERG is unmasked due to the loss of the bipolar cell response while photoreceptor function is maintained. This means that both photoreceptor function and Muller cell function can be followed by ERG in nob mice following experimentally induced optic nerve injury. We will track retinal M?ller cell and photoreceptor function using ERG and a behavioral test to measure visual acuity in mice treated with minocycline before and after experimentally induced optic nerve injury. Visual performance in an optokinetic reflex test will be used to measure visual acuity. Tissue will be collected at the end of the study to identify signaling mechanisms involved in reactive gliosis and subsequent cellular events, Clinical Significance TBI is an increasingly significant issue facing Operation Enduring Freedom and Operation Iraqi Freedom veterans. This proposal will test a treatment strategy to preserve or restore visual function to individuals with ocular injuries. In addition, we will more clearly define the role of glial cells in neural degeneration following trauma.
