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Show SCHOOL OF MEDICINE AND HEALTH SCIENCES UNDERGRADUATE RESEARCH ABSTRACTS Conclusions: The RPE is crucial in the maintenance of photoreceptors, and MCs are perhaps best positioned in the retina to respond to environmental insults and pathologies. Alterations of the complement pathway in the sCfB retina show the most dramatic metabolic response patterns in M C s and RPE. In both the RPE and MC's the CfB and C3 knockouts resulted in a decrease in the levels of most molecules probed for. In sC3 knockout samples the RPE showed increases in most molecules resulting in higher concentrations relative to n s W T mice. The sCfB knockout also showed up-regulation of many small molecules, but was unable to restore them relative to levels observed in the n s W T A similar pattern was seen for MC's. For sC3 knockout mice levels of most molecules were increased compared to nsC3 mice. However, this up-regulation failed to compensate, and concentrations of small molecules of the sC3 were still lower than the original nsWT levels. The CfB knockout had a very different effect: sCfB had continued decrease in small molecule levels relative to nsCfB. Thus the overall change was a dramatic decrease in levels from the nsWT to the sCfB conditions. This pattern suggests that there is still a mechanism for response and recovery from oxidative stress that functions with the C3 knockouts. However, the CfB knockout results in some damping of this response, as the cells are unable to reestablish molecular levels similar to those of the nsWT control. This is an interesting pattern with regards to the metabolic and physiological responses of these cell classes. Additionally, this study reveals that in pathological conditions, like exposure to cigarette smoke or when one modifies the immune functionality of a system, the variance of the metabolic signals within cell classes increases so that cell populations normally described by narrow small molecule signal profiles become more disorganized. Metabolic signals do not necessarily find new narrow metabolic meta-stable states, but the biological signals become increasingly noisy. Butler.2 - Muller Cell histograms show relative levels of molecules for smoked and non-smoked WT, CfB, C3 conditions Butler.3 - RPE histograms show relative levels of molecules for smoked and non-smoked WT, CfB, C3 conditions |
