The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes

Abstract

This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral innernuclear layer should be evaluated in early type 2 diabetic retinopathy.