科研之友
微信
新浪微博
Facebook
分享链接
摘要
Amyloid beta (A beta) is a pathogenic peptide associated with many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The retinal inflammation in response to A beta is implicated in the pathogenesis of several ocular diseases including age-related macular degeneration, Alzheimer's-related optic neuropathy and glaucoma. In the present study, we found that a single intravitreal injection of oligomeric A beta 1-40 in mouse activated the NLRP3 inflammasome and the NF-kappa B signaling, induced the production of inflammatory cytokines including TNF-alpha and IL6. In addition, A beta 1-40 caused retinal function impairment while no noticeable morphological changes were observed under light microscope. Furthermore, immunohistochemical results showed that A beta 1-40 enhanced the number of Iba1-positive cells in the inner retina. The mRNA expressions of LXRa and LXRb decreased in the neuroretina of the A beta 1-40-injected mice. No significant difference was found on the protein expressions of LXRs and ABCA1 in both neuroretina and RPE/choroid complex between the A beta 1-40-injected group and the control group. A synthetic LXR ligand, TO901317 (TO90), enhanced the expressions of LXRa and ABCA1 at both mRNA and protein levels in the A beta 1-40-injected mice, while the LXRb expression was unchanged. TO90 preserved ERG a-and b-wave amplitudes and reduced the number of Iba1-positive cells in the A beta 1-40-treated retina. Furthermore, TO90 down-regulated the mRNA levels of TNF-alpha and IL-6, as well as the expressions of pIjBa, NLRP3, caspase-1 and IL-1 beta in the A beta-1-40-injected animals. We suggest that activation of LXRa and its target gene ABCA1 exerts potent anti-inflammatory effect on the Abtreated retina.
