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Inflammatory mediators in diabetic retinopathy

Gustavsson, Carin LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:1.
Abstract
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... (More)
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-α 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. (Less)
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author
supervisor
opponent
  • Docent Kvanta, Anders, Institutionen för Klinisk Neurovetenskap, Sektionen för Ögon och Syn, Karolinska Institutet, St Eriks Ögonsjukhus, Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
inflammation, dyslipidemia, diabetic retinopathy, oxidative stress, TNF-alpha, VCAM-1
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:1
pages
192 pages
publisher
Faculty of Medicine, Lund University
defense location
MFC Jubileumsaulan, Malmö University Hospital, Entrance 59
defense date
2010-01-22 09:15
ISSN
1652-8220
ISBN
978-91-86443-15-3
language
English
LU publication?
yes
id
edb5c2e8-e544-42c0-844b-f1add5c81aa9 (old id 1516836)
date added to LUP
2010-01-05 14:32:20
date last changed
2018-05-29 10:35:21
@phdthesis{edb5c2e8-e544-42c0-844b-f1add5c81aa9,
  abstract     = {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-α 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.},
  author       = {Gustavsson, Carin},
  isbn         = {978-91-86443-15-3},
  issn         = {1652-8220},
  keyword      = {inflammation,dyslipidemia,diabetic retinopathy,oxidative stress,TNF-alpha,VCAM-1},
  language     = {eng},
  pages        = {192},
  publisher    = {Faculty of Medicine, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Inflammatory mediators in diabetic retinopathy},
  volume       = {2010:1},
  year         = {2010},
}