Protective Effect of a GLP-1 Analog on Ischemia-Reperfusion Induced
Blood-Retinal Barrier Breakdown and Inflammation.
Authors Gonçalves A, Lin CM, Muthusamy A, Fontes-Ribeiro C, Ambrósio AF, Abcouwer SF,
Fernandes R, Antonetti DA
Submitted By Steven Abcouwer on 6/17/2016
Status Published
Journal Investigative ophthalmology & visual science
Year 2016
Date Published 5/1/2016
Volume : Pages 57 : 2584 - 92
PubMed Reference 27163772
Abstract Inflammation associated with blood-retinal barrier (BRB) breakdown is a common
feature of several retinal diseases. Therefore, the development of novel
nonsteroidal anti-inflammatory approaches may provide important therapeutic
options. Previous studies demonstrated that inhibition of dipeptidyl
peptidase-IV, the enzyme responsible for the degradation of glucagon-like
peptide-1 (GLP-1), led to insulin-independent prevention of diabetes-induced
increases in BRB permeability, suggesting that incretin-based drugs may have
beneficial pleiotropic effects in the retina. In the current study, the barrier
protective and anti-inflammatory properties of exendin-4 (Ex-4), an analog of
GLP-1, after ischemia-reperfusion (IR) injury were examined.,
Ischemia-reperfusion injury was induced in rat retinas by increasing the
intraocular pressure for 45 minutes followed by 48 hours of reperfusion. Rats
were treated with Ex-4 prior to and following IR. Blood-retinal barrier
permeability was assessed by Evans blue dye leakage. Retinal inflammatory gene
expression and leukocytic infiltration were measured by qRT-PCR and
immunofluorescence, respectively. A microglial cell line was used to determine
the effects of Ex-4 on lipopolysaccharide (LPS)-induced inflammatory response.,
Exendin-4 dramatically reduced the BRB permeability induced by IR injury, which
was associated with suppression of inflammatory gene expression. Moreover, in
vitro studies showed that Ex-4 also reduced the inflammatory response to LPS and
inhibited NF-?B activation., The present work suggests that Ex-4 can prevent IR
injury-induced BRB breakdown and inflammation through inhibition of inflammatory
cytokine production by activated microglia and may provide a novel option for
therapeutic intervention in diseases involving retinal inflammation.