To study if the endogenous renin-angiotensin system affects diabetic retinal leukostasis, rats with streptozotocin-induced diabetes were treated with an ACE inhibitor (ramipril), an angiotensin II AT(1) receptor antagonist (losartan) and the Ca channel blocker, (nifedipine).
Adenovirus-mediated overexpression of adiponectin attenuated hypoxia-induced pathological retinal neovascularization by 35% in wild-type mice and by 40% in APN-KO mice and leukostasis by 64% in wild-type mice and by 75% in APN-KO mice, which were associated with reduced TNF-alpha production.
Outcome was assessed by analyzing leukostasis using fluorescein isothiocyanate coupled concanavalin A (FITC-ConA) and vessel leakage (bovine serum albumin conjugated with fluorescein isothiocyanate; FITC-BSA)/neovascularization and neurodegeneration by immunohistological approaches (hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), Brn3a).
Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARβ/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines.
Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARβ/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines.
A further study revealed hypoxic trophoblast HMGB1-induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM-1 and ICAM-1) could be reversed by pretreatment with STS.
A further study revealed hypoxic trophoblast HMGB1-induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM-1 and ICAM-1) could be reversed by pretreatment with STS.
The aim of this study was to determine whether leukostasis is present in the retina, to evaluate the levels of pigment epithelium-derived factor (PEDF) and intracellular adhesion molecule-1 (ICAM-1) levels in the blood of SDT rats, and to examine the effects of PEDF on leukostasis.
A further study revealed hypoxic trophoblast HMGB1-induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM-1 and ICAM-1) could be reversed by pretreatment with STS.
On the 15th day post-apoEdp treatment, mouse retinas were harvested to examine (1) blood-retinal-barrier (BRB) permeability by Evans blue dye, inflammatory leukostasis by concanavalin staining of leukocytes and LRP-1 pathway-related protein expression by Western blot analysis and gelatin zymography.
Outcome was assessed by analyzing leukostasis using fluorescein isothiocyanate coupled concanavalin A (FITC-ConA) and vessel leakage (bovine serum albumin conjugated with fluorescein isothiocyanate; FITC-BSA)/neovascularization and neurodegeneration by immunohistological approaches (hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), Brn3a).
Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARβ/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines.
Biochemical, genetic and functional studies strongly indicate peroxisome proliferator-activated receptor-γ (PPARγ), a pleiotropic transcription factor, as a primary target in the treatment of diabetic retinopathy.In this issue, Song et al. detail the role of PPARγ in diabetic retinopathy-related disorders, illustrating PPARγ-mediated inhibition of diabetes-induced leukostasis and leakage, and its beneficial role in modulating inflammation, angiogenesis and apoptosis in retinal and endothelial cells.
Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in the pathogenesis of DR by inhibiting diabetes-induced retinal leukostasis and leakage.