NLRP1 deficiency attenuates diabetic retinopathy (DR) in mice through suppressing inflammation response
- Central South University, Changsha 410083, Hunan Province (China)
- Beijing Aier-Intech Eye Hospital, Panjiayuan Plaza, No.12 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China)
- The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province (China)
Highlights: • NLRP1 expression was increased in retina of diabetic mice. • NLRP1 deletion attenuates STZ-induced diabetic retinopathy. • Knockout of NLRP1 reduces inflammation and alleviates diabetic retinopathy in STZ mice. • Suppression of NLRP1 restrains inflammation in high fructose-incubated retinal ganglion cells. 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 NLRP1{sup −/−} mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRP1{sup −/−} significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in retinas. NLRP1{sup −/−} ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1{sup −/−}/DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRP1{sup −/−}. In addition, vascular endothelial growth factor (VEGF) and Iba1 expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1{sup −/−}/DR mice. Consistently, NLRP1{sup −/−} attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1{sup −/−} 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.
- OSTI ID:
- 23137046
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 501, Issue 2; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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