Characterization of corneal and retinal changes in a metabolic syndrome model in young and adult mice

INTRODUCTION: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities, such as central obesity, insulin resistance, dyslipidemia, and hypertension. One of the main characteristics of MetS is the presence of a chronic proinflammatory state, which activates the nuclear factor of activated T cells 5 (NFAT5) in response to the hyperosmolar state. METHODOLOGY: A MetS model was generated in C57BL/6 mice fed to a high-sucrose diet for 120 days. Subsequently, clinical and biochemical parameters were evaluated to confirm MetS. Microvascular changes, histological analysis and the presence of proteins related to NFAT5 activity in inflammation (NLRP3, capase-1) and neurodegeneration (GAP43, GFAP) were evaluated in cornea and retinal tissues. RESULTS: MetS seems to accelerate the aging process, as young individuals with MetS exhibit characteristics typically seen in normal-weight adults, causes changes in the microvasculature, increasing the in vivo arteriole-to-venule ratio (AVR), in addition to causing NFAT5 relocalization in the retina, which triggers an increase in the inflammasome via NLRP3/caspase-1, in addition to decreasing the presence of GAP43 and GFAP. However, in the cornea, the behavior of NFAT5 is similar, as it relocalizes, but the inflammasome is not fully expressed. Similarly, the levels of the molecules involved in the development of dry eye syndrome, AQP5 and GAP43, are decreased. CONCLUSIONS: Our results revealed a close relationship between MetS and ocular alterations associated with chronic systemic inflammation, which seems to play a central role in the development of these ocular complications.