Date of Award
2010
Degree Type
Thesis
Degree Name
Master of Science
Program
Pathology
Supervisor
Dr. Subrata Chakrabarti
Second Advisor
Dr. Chandon Chakraborty
Third Advisor
Dr. Hao Wang
Abstract
Despite the identification of multiple pathogenetic mechanisms in a complex problem like diabetic retinopathy (DR), limited success has been achieved in its medical treatment. Vascular endothelial cells (ECs) undergo a series of metabolic changes in response to sustained hyperglycaemia in diabetes. These metabolic derangements cause the activation of transcription factors and augmented expression of several growth factors and vasoactive factors including vascular endothelial growth factor (VEGF), resulting in structural and functional alteration in the retina. Small, non-protein coding miRNAs are endogenous regulators of gene expression and have been implicated in a variety of cellular physiologic and pathologic processes. In this study, we investigated whether miRNA alterations play a key role in DR. We show a direct relationship between miR-200b and VEGF in vascular ECs exposed to hyperglycemic conditions. Glucose caused downregulation of miRNA-200b resulting in an increase in VEGF expression. We also show that this relationship exists in the retina of animal and human diabetes. We further demonstrated that diabetes induced VEGF-mediated structural and functional changes in the ECs and in retina can be blocked through increasing miR-200b. This study establishes the potential treatment of DR through a miRNA based approach.
Recommended Citation
McArthur, Kara, "microRNA-200b MODULATES VEGF EXPRESSION IN DIABETIC RETINOPATHY" (2010). Digitized Theses. 4175.
https://ir.lib.uwo.ca/digitizedtheses/4175