Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8292535 | Biochemical and Biophysical Research Communications | 2018 | 7 Pages |
Abstract
Diabetic retinopathy (DR) is the common cause of diabetic vascular complications. The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known as NALP1, inflammasome is the first member of the NLR family to be discovered, playing an important role in inflammatory response. However, its effect on DR development has not been reported. In the study, the wild type (WT) and NLRP1â/â mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRP1â/â significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in retinas. NLRP1â/â ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1â/â/DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRP1â/â. In addition, vascular endothelial growth factor (VEGF) and Iba1 expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1â/â/DR mice. Consistently, NLRP1â/â attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1â/â markedly decreased retina p-nuclear factor-κB (NF-κB), interleukin-1β (IL-1β) and IL-18 levels. And similar results were confirmed in vitro that suppressing NLRP1/ASC inflammasome ameliorated inflammatory response in fructose-treated retinal ganglion cells. The results above indicated that the modulation of NLRP1 inflammasome might be a promising strategy for DR therapy.
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Authors
Yan Li, Chang Liu, Xin-Shun Wan, Shao-Wei Li,