Dysregulation of the NLRP3 Inflammasome in Diabetic Retinopathy and Potential Therapeutic Targets

Abstract

Diabetic Retinopathy (DR) is an insidious neurovascular disorder secondary to chronic glycemic dysregulation in elderly diabetic patients. In the later stages of DR, the disease manifests as fluid infiltrating the macula, culminating in the leading cause of irreversible visual impairment in working age adults. With the current mainstay treatments preoccupied with slowing down the progression of DR, this presents an unsustainable solution from both an economic and quality of life perspective. Although the exact mechanisms by which hyperglycemia leads to retinal tissue insult are unknown, the evidence suggests that chronic low-grade inflammation in diabetic eye is in part driving the constellation of symptoms present in DR. Of the innate immune system within the eye, the NLR Family Pyrin Domain Containing 3 Inflammasome (NLRP3) has been identified in retinal cells as a causal factor in the pathogenesis of DR. Multiple pathways appear to be present in the diabetic eye that instigate prolonged activation of the NLRP3 which subsequently exerts its deleterious effects by upregulating the release of Interleukin-1Beta and Interleukin-18. In this review, we highlight the current understanding of the pathophysiology of DR, the dysregulation of the NLRP3 secondary to hyperglycemic stress in retinal cells, and novel therapeutic targets to alleviate overactivation of the inflammasome.