Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.593270
Title: The role of transforming growth factor beta and other growth factors in the development of diabetic retinopathy
Author: Pascal, M. M.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1998
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Abstract:
The present study showed that TFG-β mRNA and protein expression is regulated by glucose concentration in HREC. Maximal secreted protein levels and mRNA were produced at a concentration of 15 mM and the majority of the TGF-β is found in an active form in these cells. These results were novel and specific as HREC have not been shown before to express TFG-β in response to glucose. TGF-β appears to be central to a wide range of pathological features involved in the disease and this first study highlights a possible important role for TGF-β in the mechanism of induction of microvascular abnormalities in the retina. It could also play a role as a key mediator of the high glucose induced effects in DR, as is the case in the kidney. Glucose dependent changes in TGF-β receptors expression and signalling intermediates were also examined in HREC. These studies indicate that glucose is able to regulate both TGF-β expression and the receptor numbers of affinity but it is apparent that there is no simple correlation between secreted TGF-β and receptor number or affinity or expression. Protein kinase C isoforms protein expression did not change relatively to glucose but various isoforms were expressed at different intensities in endothelial cells and TGF-β signalling cascade involves a MAPK independent pathway. TGF-β expression in the ganglion cell layer demonstrated a neurotrophic role for TGF-β, whereas VEGF expression did not seem to correlate spatially or temporally with angiogenesis. We suggest that both systemic cells (PBLs) and endothelial cells are able to secrete a wide range of growth factors when activated by glucose. These factors, along with other ones (platelet derived growth factor or insulin like growth factor type 1), may act in synergy to produce an imbalance in growth factor levels which could lead to angiogenesis and therefore contribute to the pathogenesis of PDR.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.593270  DOI: Not available
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