Dectin-1 Drives Diabetic Retinopathy via Inducing Microglia-Mediated Inflammation and Blood–Retinal Barrier Breakdown

Abstract

Diabetic retinopathy (DR), a prevailing manifestation among diabetic patients, occurs as a major sight-threatening disorder. Dectin-1, as an innate immune receptor, has been notified as a critical modulator of diabetes mellitus. In this context, the implication of Dectin-1 in the process of DR that is still a conundrum will be addressed here. The diabetic mouse model was established by intraperitoneal injection of streptozotocin (STZ), and human microglia cells (HMC3) were subjected to high glucose (HG) to create cellular models of diabetes. Glucose level and body weight were recorded in mice. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting checked Dectin-1 expression. RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and western blotting appraised the inflammatory levels. Immunofluorescence staining and western blotting ascertained the expression of IBA-1 and tight junction proteins. Besides, western blotting also examined albumin expression. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and western blotting assayed the apoptotic level. Dectin-1 was highly expressed in both retinal tissues of diabetic mice and HG-exposed HMC3 cells. Dectin-1 antagonist laminarin (LAM) observably repressed microglia activation, inflammatory reaction, and blood–retinal barrier (BRB) leakage both in vitro and in vivo. Moreover, LAM produced anti-apoptotic effect in vivo. To sum up, Dectin-1 inhibitor might block the inflammatory cascade and protect against BRB disruption in DR.