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Purification and characterisation of endothelial migration factor(s) in the serum of patients with diabetic retinopathy

Proliferative diabetic retinopathy (PDR) is a major cause of blindness. In the present study the possible role of systemic growth factors on the migration and proliferation of retinal endothelial cells (EC) was examined. These studies show that patients with active PDR have a serum activity which stimulates the migration but not the proliferation of retinal EC, and that this activity is not diminished in plasma-derived serum (PDS). A strong correlation was observed between migratory activity in the serum and serum platelet-derived growth factor (PDGF) levels, while antibodies to PDGF partially inhibited the stimulatory effect of PDR serum. However, retinal EC failed to respond to purified PDGF in isolation. These was also an attempt to characterise the activity in PDR sera. The results indicate that the activity (a) is retained in a fraction of serum with a molecular weight between 10 and 30kd, (b) can be eluted from a Q-Sepharose column with 20-30% NaCl (c) has a pI of 5.8 and (d) is retained by passage down a Heparin-Sepharose column from which it could be eluted with 1.2M NaCl. The hypothesis that serum migration activity is due to synergism between PDGF and the HBGF, FGF was tested, and the <I>in vitro</I> results show that constant concentration of PDGF (25pM) combined with aFGF (1.0-1000fg/ml), but not, bFGF synergised to stimulate EC migration. It is suggested that systemic cells such as lymphocytes exposed to non-physiological glucose levels can be activated to secrete a wide range of growth factors which could be detected in the serum. These factors may include both the HBGF and PDGF which may synergise and contribute to the pathogenesis of PDR.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:593411
Date January 1995
CreatorsShafiee, Afshin
PublisherUniversity of Aberdeen
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU078842

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