Tanique McDonald - PhD Candidate, Neuroscience Graduate Program
Schizophrenia is a chronic neuropsychiatric disorder that causes severe cognitive and functional impairments and is associated with premature mortality. In conjunction with the debilitating hallmark symptoms (i.e., delusions, hallucinations, and disorganized speech), schizophrenia is also associated with a range of visual deficits that alter perception and contribute to delusion formation. Notable visual system changes include retinal atrophy, reduced retinal signaling, altered contrast sensitivity, and reduced surround suppression. Like the overall disorder, the cause of these visual deficits remains unknown. However, an emerging body of literature suggests that elevated levels of the inflammatory cytokine, TNFa, triggers apoptosis of retinal ganglion cells, which is associated with degenerative effects along the feedforward visual pathway. These neuroprogressive effects are consistent with the aforementioned visual deficits commonly observed in patients with schizophrenia. Additionally, prior research has revealed elevated ocular and systemic levels of TNFa in patients with schizophrenia. Despite this, the link between ocular inflammation and visual deficits in schizophrenia remains speculative. The central hypothesis of this proposal is that there are significant positive relationships between higher ocular TNFa concentrations and the visual system changes commonly observed in patients with schizophrenia. Experiments proposed in Aim 1 will quantify ocular TNFa levels in patients and correlate these findings with measurements of retinal structure, visual system processing, and visual perception. Experiments proposed in Aim 2 will use a newly developed Mustela putorius furo (ferret) model to specify mechanistic electrophysiological changes to early components of the visual system (retina, visual thalamus, primary visual cortex) following exacerbation of ocular inflammation via TNFa. The proposed translational study will clarify the cellular and electrophysiologic bases for specific visual system deficits and validate the first animal model of visual anatomical and perceptual impairments in schizophrenia. This work also has potential implications for the development of biomarkers for early detection and monitoring of neuroprogression, and for animal modeling and other research strategies addressing visual system changes associated with neurodegenerative, and psychosis-related disorders.
Oct 11, 2024 @ 2:00 p.m.
Medical Center | K207 (2-6408)
Host: Advisors: Farran Briggs, PhD and Steven Silverstein, PhD