Graduation Year
2019
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Cesario V. Borlongan, Ph.D.
Committee Member
Jay B. Dean, Ph.D.
Committee Member
Toru Shimizu, Ph.D.
Committee Member
Chuanhai Cao, Ph.D.
Committee Member
Byeong Jake Cha, Ph.D.
Committee Member
Ken Arai, Ph.D.
Keywords
Mesenchymal stem cells, Mitochondria, Retinal Ischemia, Stroke
Abstract
Stoke is a leading cause of disability and mortality across the globe, making it a global health crisis. However, treatments for stroke remain limited with narrow therapeutic time window. Visual impairment negatively affects patients’ quality of life. During stroke, the disruption in blood flow might affect both brain and eye resulting in cerebral and retinal ischemia. Currently, there is a lack of treatment option that targets both cerebral and retinal ischemia. Ischemic stroke pathology is complex and multiphasic. The ischemic event is followed by a secondary cascade of inflammatory cytokines exacerbating the initial focal injury and expanding into the penumbra. In recent years, mitochondrial dysfunction has been identified as a hallmark pathological of ischemia and reperfusion injuries. This pathology is marked by an increase in oxidative stress and reduced oxidative phosphorylation. Investigations have begun to shine the spotlight on mitochondrial dysfunction as the key contributor in stroke pathology. The role of stem cells as a therapeutic option has been growing over the last decade, particularly in central nervous system disorders. However, the underlying therapeutic mechanisms of stem cell therapy remain elusive. In the present work, we investigated the role of mitochondrial dysfunction as a key mechanism of cell death in stroke-induce retinal ischemia and explored the therapeutic mechanism of stem cell to rescue the mitochondrial dysfunction. We demonstrated that retinal ischemia accompanied cerebral ischemia, causing cellular degeneration in the eye. We showed that mitochondrial dysfunction characterized by decreased mitochondrial function, altered mitochondrial network morphology, and imbalanced mitochondrial dynamics, altogether indicating that impaired mitochondria are a key contributor to ischemic cell death. Finally, we demonstrated that stem cell therapy is a potential treatment for retinal ischemia by rescuing mitochondrial dysfunction via transfer of healthy mitochondria to injured cells. The present work revealed that using stem cells to target mitochondrial dysfunction represents a potential therapy for cerebral and retinal ischemia and potentially for other CNS disorders with mitochondrial dysfunction as a rampant underlying pathology.
Scholar Commons Citation
Nguyen, Hung Vu Thien, "An Eye Opener in Stroke: Mitochondrial Dysfunction and Stem Cell Repair in Stroke-induced Retinal Ischemia" (2019). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/8396
