eprintid: 10123358
rev_number: 8
eprint_status: archive
userid: 695
dir: disk0/10/12/33/58
datestamp: 2021-03-05 11:48:49
lastmod: 2021-03-05 11:48:49
status_changed: 2021-03-05 11:48:49
type: thesis
metadata_visibility: show
creators_name: Hyer, Stephen Laurence
title: Growth hormone and tissue growth factors in the pathogenesis of diabetic retinopathy
ispublished: unpub
note: Thesis digitised by ProQuest.
abstract: The aim of this work was to examine the role of Growth Hormone (GH) and tissue growth factors in the pathogenesis of diabetic retinopathy, and to investigate the mechanism of excessive GH secretion in diabetes. Levels of GH and insulin-like growth factor-I (IGF-I) (the principal mediator of the growth promoting activity of GH) were measured in diabetic patients with retinopathy and control subjects. The concentration of basic fibroblast growth factor (bFGF), a potent angiogenic growth factor, was also examined in vitreous and retinal extracts. 24h studies confirmed increased GH and normal IGF-I levels during poor diabetic control suggesting impaired IGF-I production. Serum IGF-I was inversely correlated with HbA1 concentration. Reduced feedback inhibition by IGF-I when control is poor could contribute to excessive GH release. In addition, pretreatment with GH failed to suppress the GH response to GH-releasing hormone (GHRH) in some patients indicating altered GH feedback control. Relative resistance to somatostatin was inferred from the results of treatment with octreotide, a potent somatostatin analogue. GH hypersecretion in diabetes is likely to be a product of several different mechanisms. No correlation was found between the development of background retinopathy and changes in serum IGF-I concentration, in patients commencing continuous subcutaneous insulin infusion. A significant increase in mean serum IGF-I occurred at the onset of proliferative retinopathy in patients treated conventionally (281 ± 54 versus 196 ± 58 micrograms/l; p <0.05). Cultured retinal endothelial cells were demonstrated to release IGF-I but not bFGF into the cell medium. A different release mechanism is likely for bFGF which was abundant in whole retinal extracts. In the diseased diabetic retina, cell damage could release bFGF which would then induce cell competence in surviving endothelial cells and fibroblasts. By allowing the cells to complete the cell cycle, the increase in IGF-I levels could play a crucial role in promoting cell proliferation and neovascularisation.
date: 1990
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: M.D
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
full_text_status: public
pages: 311
institution: UCL (University College London)
department: Department of Medicine
thesis_type: Doctoral
citation:        Hyer, Stephen Laurence;      (1990)    Growth hormone and tissue growth factors in the pathogenesis of diabetic retinopathy.                   Doctoral thesis  (M.D), UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10123358/1/Growth_hormone_and_tissue_grow.pdf