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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1076/ceyr.22.3.190.5519 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Endothelial lipase-binding peptides similar to netrin-1 inhibit hepatitis B virus infection.
FEBS Lett
January 2025
Research Department, Purotech Bio Inc, Yokohama, Japan.
Hepatitis B virus (HBV) infects cells by attaching to heparan sulfate proteoglycans (HSPG) and Na/taurocholate cotransporting polypeptide (NTCP). The endothelial lipase LIPG bridges HSPG and HBV, facilitating HBV attachment. From a randomized peptide expression library, we identified a short sequence binding to LIPG.
View Article and Find Full Text PDFD1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders.
Mol Psychiatry
January 2025
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli, 80078, Naples, Italy.
Lysosomal storage disorders characterized by defective heparan sulfate (HS) degradation, such as Mucopolysaccharidosis type IIIA-D (MPS-IIIA-D), result in neurodegeneration and dementia in children. However, dementia is preceded by severe autistic-like behaviours (ALBs), presenting as hyperactivity, stereotypies, social interaction deficits, and sleep disturbances. The absence of experimental studies on ALBs' mechanisms in MPS-III has led clinicians to adopt symptomatic treatments, such as antipsychotics, which are used for non-genetic neuropsychiatric disorders.
View Article and Find Full Text PDFElevated glycocalyx shedding components as the early predictors of unfavorable outcomes in patients after cardiac arrest: A single-center observational study.
J Crit Care
January 2025
Department of Emergency Medicine Center, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China. Electronic address:
Objective: To assess the association of serum glycocalyx shedding components (Heparan sulfate, HS; Hyaluronic acid, HA; Syndecan-1, Sdc-1) with outcomes after CA.
Methods: Patients who were comatose for >24 h after CA in the intensive care unit (ICU) of the Affiliated Hospital of Xuzhou Medical University from 9/2021 to 04/2023 were enrolled. Serum samples were collected 24 h after CA to measure the concentrations of glycocalyx shedding components.
Screening of Insertion Sites and Tags on EV-A71 VP1 Protein for Recombinant Virus Construction.
Viruses
January 2025
Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200433, China.
This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus's infectivity and replication can be assessed by measuring postinfection luciferase signals.
View Article and Find Full Text PDFA Review of the Utility of Established Cell Lines for Isolation and Propagation of the Southern African Territories Serotypes of Foot-and-Mouth Disease Virus.
Viruses
December 2024
Department of Biological Sciences and Biotechnology, School of Life Sciences, Botswana International University of Science and Technology, Private Bag 16, Palapye 10071, Botswana.
Cell culture underpins virus isolation and virus neutralisation tests, which are both gold-standard diagnostic methods for foot-and-mouth disease (FMD). Cell culture is also crucial for the propagation of inactivated foot-and-mouth disease virus (FMDV) vaccines. Both primary cells and cell lines are utilised in FMDV isolation and propagation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!