Inflammatory mediators in diabetic retinopathy
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1516836
- author
- Gustavsson, Carin LU
- supervisor
- opponent
-
- Docent Kvanta, Anders, Institutionen för Klinisk Neurovetenskap, Sektionen för Ögon och Syn, Karolinska Institutet, St Eriks Ögonsjukhus, Stockholm
- organization
- publishing date
- 2010
- 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 09:15:00
- ISSN
- 1652-8220
- ISBN
- 978-91-86443-15-3
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Ophthalmology (013242810), Unit on Vascular Diabetic Complications (013241510)
- id
- edb5c2e8-e544-42c0-844b-f1add5c81aa9 (old id 1516836)
- date added to LUP
- 2016-04-01 15:01:36
- date last changed
- 2023-04-18 20:02:27
@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}},
keywords = {{inflammation; dyslipidemia; diabetic retinopathy; oxidative stress; TNF-alpha; VCAM-1}},
language = {{eng}},
publisher = {{Faculty of Medicine, Lund University}},
school = {{Lund University}},
series = {{Lund University Faculty of Medicine Doctoral Dissertation Series}},
title = {{Inflammatory mediators in diabetic retinopathy}},
url = {{https://lup.lub.lu.se/search/files/4304952/1516837.pdf}},
volume = {{2010:1}},
year = {{2010}},
}