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Title: A Study of Endothelial Progenitor Cell Dynamics during Diabetic Retinopathy
Author: Bhatwadekar, A. D.
ISNI:       0000 0001 3463 4149
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Progressive vasodegeneration is the characteristic feature of diabetic retinopathy (DR). The resultant retinal ischaemia leads to sight-threatening neovascularisation and macular oedema. Vascular repair by bone marrow-derived endothelial progenitor cells (EPCs) is known to be impaired in dfabetes; however the role of EPCs in DR remains ill-defined. This thesis is based on the hypothesis that accumulation of advanced glycation end products (AGEs) on capillary basement membranes (BMs), as occurs during DR, could hamper EPCs vasoreparative function in this specialised microvascular bed. To explore the present aims, EPCs isolated from peripheral blood were characterized by immunocytochemistry and flow Cytometry and propagated on AGE substrates akin to those found in diabetes. AGE-modification of vascular substrates impaired EPC adhesion, spreading and migration while restoration of key arginine motif reversed this impairment. This aspect was conclusively extrapolated in novel in vitro model in which highly delineated regions of endothelial' apoptosis were created using combination of photodynamic drug verteporfin and red light. EPCs successfully repaired wounds under normal conditions however AGE modification of 8M showed inability of EPC to adhere and incorporate into resident endothelium. It was also found that apoptotic endothelial bodies/cells and EPCs interactions facilitated EPC recruitment. This was perhaps due to the upregulation of adhesion molecule expression and by increase of pro-inflammatory cytokines. In aparallel study we showed that blockage of the receptor for AGEs (RAGE) shows protection against vascular lesion as exhibited by decrease in acellular capillaries and improvement in pericyte numbers. In addition RAGE blockage controlled inflammatory activation of MOiler cells and microglia. Taken together, the findings of this thesis suggest that EPCs could playa hitherto unrecognised role in retinal capillary endothelial repair which may have important implications for progressive vasodgeneration during DR.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available