Vascular localization of heparan sulfate proteoglycans in retinas of patients with diabetes mellitus and in VEGF-induced retinopathy using domain-specific antibodies

Autor: A. N. Witmer, Gijs F.J.M. Vrensen, J. van den Born, Reinier O. Schlingemann
Přispěvatelé: Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT), Other departments
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Vascular Endothelial Growth Factor A
Fluorescent Antibody Technique
Vascular permeability
Heparitin Sulfate/metabolism
Endothelial Growth Factors
Diabetes Mellitus/metabolism
Immunoenzyme Techniques
chemistry.chemical_compound
Antibody Specificity
Blood-Retinal Barrier
80 and over
Fluorescent Antibody Technique
Indirect
Heparan Sulfate Proteoglycans/metabolism
Aged
80 and over
Agrin
Retinal Vessels/drug effects
Heparan sulfate
Middle Aged
Sensory Systems
Vascular endothelial growth factor
Vascular endothelial growth factor A
medicine.anatomical_structure
Diabetic Retinopathy/chemically induced
Agrin/metabolism
Retinopathy
medicine.medical_specialty
Indirect
Blood–retinal barrier
Perlecan
Biology
Endothelial Growth Factors/toxicity
Capillary Permeability
Cellular and Molecular Neuroscience
Internal medicine
Diabetes Mellitus
medicine
Animals
Humans
Aged
Diabetic Retinopathy
Animal
Retinal Vessels
medicine.disease
carbohydrates (lipids)
Ophthalmology
Disease Models
Animal
Macaca fascicularis
Endocrinology
chemistry
Disease Models
biology.protein
Heparitin Sulfate
Heparan Sulfate Proteoglycans
Zdroj: Current Eye Research, 22(3), 190-197
Current eye research, 22(3), 190-197. Taylor and Francis Ltd.
ISSN: 0271-3683
Popis: PURPOSE: The Steno hypothesis (Deckert et al. ) states that in diabetes mellitus (DM), changes in vascular heparan sulfate proteoglycan (HSPG) expression are involved in systemic endothelial dysfunction and increased capillary permeability. In diabetes-induced glomerular capillary leakage, loss of HSPG and its side chains has been documented. This study aimed to investigate whether microvascular leakage in diabetic retinopathy (DR) is also associated with altered expression of HSPG in retinal microvessels.METHODS: Serial cryosections of post-mortem eyes of 22 subjects with DM and 7 controls were stained with antibodies against the core proteins of the basement membrane HSPGs agrin (Abs Bl31 and JM72) and perlecan (Ab 1948), and four antibodies against heparan sulfate side chains (HS) (Abs JM403, HepSS1, JM13, 3G10). Moreover, we investigated Cynomolgus monkey eyes injected with vascular endothelial growth factor (VEGF)-A, as a model of retinal microvas-cular leakage. The endothelial antigen PAL-E was used to detect microvascular leakage.RESULTS: In the retina of all controls and DM cases, agrin and perlecan core proteins and HS as recognized by JM403 and 3G10 were expressed in the walls of microvessels. Staining for JM13 was variable between cases, but unrelated to microvascular leakage as determined by PAL-E. Staining for HepSS1 was absent in all human retinal microvessels. In monkey retinas, HSPG staining was identical to that in human retinal tissues, except for the staining for HepSS1, which was found absent in control monkey eyes but which was positive in VEGF-injected eyes.CONCLUSIONS: Increased microvascular permeability in human DR is not associated with changes in expression of the HSPGs studied, whereas high amounts of VEGF may induce increased expression of the HS side chain epitope recognized by HepSS1. These results suggest that the mechanism underlying retinal leakage is different from diabetic glomerular capillary leakage.
Databáze: OpenAIRE
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