NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes.

ABSTRACT

Ischemic stroke remains a devastating disease which is the leading cause of death worldwide. Visual impairment after stroke is a common complication which may lead to vision loss, greatly impacting life quality of patients. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood flow to the eye, resulting in retinal ischemia and leading to visual impairment. Diabetes increases the risk of ischemic stroke and induces diabetic retinopathy; the latter may be more sensitive to the ischemic retinal injury. In diabetic status, the underlying mechanism in stroke-induced retinal injury has not been fully clarified. The NLR pyrin domain containing 3 (NLRP3) inflammasome is an important activator of inflammation, which may play a critical role in catalyzing and forming certain pro-inflammatory cytokines in both cerebral and retinal ischemia. Isoflurane has been demonstrated to inhibit the activation of the NLRP3 inflammasome and show neuroprotective effects. In this study, we established a diabetic mouse model and performed the middle cerebral artery occlusion procedure to induce ischemic stroke. Our results revealed that cerebral ischemia-induced retinal injury in the diabetic model. Isoflurane pretreatment alleviated the cerebral and retinal injury after ischemic stroke. Of note, isoflurane pretreatment inhibited the NLRP3 inflammasome activation in the retina, indicating that isoflurane pretreatment may provide substantial retinal protection in stroke-induced retinal injury in diabetes.