Tanique McDonald^1,2,3, Steven Silverstein^1,2,3,4, Farran Briggs^1,5; ¹Department of Neuroscience, University of Rochester Medical Center Rochester, New York 14642, ²Center for Visual Science, University of Rochester, Rochester, New York 14627, ³Department of Psychiatry, University of Rochester Medical Center, Rochester, New York 14642, ⁴Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York 14542, ⁵National Eye Institute, National Institutes of Health, Bethesda, Maryland, 20892

Schizophrenia is a severe neuropsychiatric disorder that is characterized by multiple visual system changes. The causes of these changes are unknown, however elevated systemic levels of TNF⍺, an inflammatory cytokine, have been reported in drug-naïve, first-episode schizophrenia patients. When released by microglia in the retina, TNF⍺ is known to promote the death of retinal ganglion cells which in turn has been linked to degenerative effects along the feedforward visual system pathway, some of which are consistent with altered visual response properties frequently observed in people with schizophrenia.In this study, we report on a new animal (ferret) model that tests the hypothesis that retinal neuroinflammation can generate many of the visual system changes observed in people with schizophrenia. Using optical coherence tomography and single-neuron recordings, we are assessing the structural and functional alterations to early visual structures (retina, visual thalamus, primary visual cortex) following the elevation of TNF⍺ levels in the eye after intravitreal injection.Preliminary results suggest that loss of retinal cells depends on the concentration of TNF⍺ injected as well as the time between injection and neuronal recordings. Moreover, following intravitreal injection of TNF⍺, significant retinal hypertrophy was observed as well as altered visual response properties including reduced firing rates, elevated contrast sensitivity and altered spatial and temporal frequency preferences for contralesional cells of the lateral geniculate nucleus.With this study, we aim to use a ferret model of elevated ocular inflammation to explore the neural mechanisms underlying perceptual deficits in schizophrenia at different stages of disease progression.