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Inflammatory mediators in diabetic retinopathy

by Gustavsson, Carin, PhD

Abstract (Summary)
Diabetic retinopathy (DR) is the most feared complication of diabetes with an overall prevalence of 21.9-36.8% and may, if untreated, lead to severe visual disability or blindness. DR is histologically characterized by pericyte and endothelial cell loss, formation of acellular vessel strands, micro-occlusions, progressive ischemia, and finally the appearance of neovascularization and fibrosis. Hyperglycemia in the retina activates pro-inflammatory pathogenetic pathways i.e., the polyol, PKC, hexosamine, and RAS pathways, as well as AGE formation. Molecular changes result in blood flow alterations, formation of reactive oxygen species and oxidative stress, induction of inflammatory signaling systems and inflow of leukocytes, and ultimately altered gene transcription, in turn promoting the biomolecular DR characteristics. This thesis enlightens how established pathways may contribute to inflammation in DR and summarizes the results of five studies. Up-regulation of inflammatory mediators and leukocyte adhesion molecules was demonstrated in serum and eyes of diabetic subjects with both proliferative DR and no or non-proliferative DR in humans. The roles of oxidative stress as well as of inflammation in retinal ischemia-reperfusion were assessed in rats with and without diabetes, while retinal endothelial expression of VCAM-1 and leukocyte accumulation were studied in early diabetes in mice. Dyslipidemia and the anti-inflammatory effects of lipid-modulating compounds as well as an immunoregulating role of TNF-? were also analyzed. These studies support that inflammation, which might be aggravated by dyslipidemia, has a role in early as well as late stages of DR.
Bibliographical Information:

Advisor:

School:Lunds universitet

School Location:Sweden

Source Type:Doctoral Dissertation

Keywords:MEDICINE; dyslipidemia; inflammation; diabetic retinopathy; oxidative stress; TNF-alpha; VCAM-1

ISBN:978-91-86443-15-3

Date of Publication:01/01/2010

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