Understanding The Role Of Transforming Growth Factor-β Activated Kinase-1 During Inflammation in Diabetic Retinopathy

dc.contributor.advisorBelecky-Adams, Teri
dc.contributor.authorPoudel, Umanga
dc.contributor.otherSlayback-Barry, Denise
dc.contributor.otherDai, Guoli
dc.date.accessioned2025-01-14T09:02:37Z
dc.date.available2025-01-14T09:02:37Z
dc.date.issued2024-12
dc.degree.date2024
dc.degree.disciplineDepartment of Biologyen
dc.degree.grantorIndiana University
dc.degree.levelM.S.
dc.descriptionIUI
dc.description.abstractThe role of microglial TAK1 in inflammation during diabetic retinopathy is not well understood but is known to affect the health of neurovascular units through the activation of inflammatory factors and cytokines. Loss in barrier activity in the neurovascular unit leads to leukocyte infiltration leading to the activation of microglia. The role of TAK1 was investigated in murine retinal microglial cultures in vitro by looking into the activation of TAK1 and downstream MAP kinase p38 activated by the treatment of pro-inflammatory factors; LPS and TNF-α, through western blotting. Treatment with LPS showed negative regulation of p38 by TAK1 in vitro in cells treated in non-diabetic conditions. Under conditions that mimicked hyperglycemia, TAK1 activation was not seen in murine retinal microglia treated with pro-inflammatory factor; LPS 20ng/ml or TNF-α 50pg/ml for 1hr. Moreover, there were no significant changes in murine retinal microglia treated with TAK1i subsequently after LPS 20ng/ml treatment for 1hr. On the contrary, the downstream MAPK p38 activation was not seen in murine retinal microglia treated in conditions that mimicked hyperglycemia while it showed significant response to changes in osmolarity. The in vivo study in retinal flat mounts showed TMEM119 as a potential candidate that could drive the td-Tomato expression in murine retinal microglia as 95% of the cells were colabelled with murine retinal microglia td-Tomato driven by TMEM119 and IBA1 which was further supported by the conditional TAK1 knockout experiment which showed 95% of the cells had TAK1 knocked out from the murine retinal microglia, confirming TMEM119 as excellent candidate for protein expression in murine retinal microglia.
dc.identifier.urihttps://hdl.handle.net/1805/45267
dc.language.isoen_US
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectmicroglia
dc.subjectdiabetic retinopathy
dc.subjectdiabetes
dc.subjectinflammation
dc.subjectretina
dc.titleUnderstanding The Role Of Transforming Growth Factor-β Activated Kinase-1 During Inflammation in Diabetic Retinopathy
dc.typeThesisen
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