Back to Search
Start Over
The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen‐induced retinopathy
- Source :
- The FASEB Journal. 26:1100-1109
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- Leukotrienes have been implicated in the pathogenesis of degenerative diabetic retinopathy, with research focusing primarily on leukotriene B(4), with little attention devoted to the cysteinyl leukotrienes (cysLTs), which act through cysLT receptors (CysLT(1)R and CysLT(2)R). We demonstrate here the presence of CysLT(2)R in pericytes and endothelial cells of superficial retinal vasculature using an indirect assay by assessment of β-galactosidase expression in CysLT(2)R-knockout (KO) mice. Retinal damage was induced in KO and wild-type (WT) mice using an established oxygen-induced retinopathy (OIR) model. CysLT(2)R expression following OIR was intensely up-regulated compared to sham-treated controls. Staining with Griffonia simplicifolia lectin revealed enhanced tissue damage (as assessed by vasoobliteration/vasoproliferation) in KO mice compared to WT controls, yet the opposite was true with respect to retinal edema. However, vascular endothelial growth factor receptor 1 (VEGFR1) transcripts were increased by OIR similarly with respect to genotype. Intravitreal application of exogenous cysLTs elicited greater vasculature leakage (assessed ex vivo) in eyes from WT mice compared to KO mice. While mRNA encoding enzymes for various components of the leukotriene cascade were detected in sham- and OIR-treated retinas, only prostaglandins and hydroxyeicosatetraenoic acids, but not leukotrienes, were detected in A23187-treated retina preparations. Together, these results implicate the CysLT(2)R in the progression of ischemic retinopathy.
- Subjects :
- Gene Expression
Retinal Neovascularization
Biochemistry
Mice
chemistry.chemical_compound
0302 clinical medicine
Hydroxyeicosatetraenoic Acids
Receptor
Calcimycin
Mice, Knockout
0303 health sciences
Leukotriene
Reverse Transcriptase Polymerase Chain Reaction
Chemistry
Immunohistochemistry
Calcium Ionophores
medicine.anatomical_structure
Pericyte
medicine.symptom
Papilledema
Biotechnology
Retinopathy
Leukotrienes
medicine.medical_specialty
Endothelium
Mice, Transgenic
Inflammation
Retina
Capillary Permeability
03 medical and health sciences
Retinal Diseases
Albumins
Internal medicine
Genetics
medicine
Animals
Cysteine
Molecular Biology
030304 developmental biology
Receptors, Leukotriene
Vascular Endothelial Growth Factor Receptor-1
Retinal
medicine.disease
Mice, Inbred C57BL
Oxygen
Disease Models, Animal
Endocrinology
Prostaglandins
Endothelium, Vascular
Pericytes
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....9ceee62e26ecd4db8b16165cd9cdf104