Work

High-density lipoprotein alleviates ocular inflammation by downregulating M1 microglia and pyroptosis through regulating lipid accumulation and Caveolin-1 expression

Year: 2024

Type: article

Abstract: • HDL deficiency is linked to uveitis, yet its role in intraocular inflammation is not fully understood. • HDL suppresses ocular inflammation, restores retinal function, and shifts microglia from M1 to M2 phenotype. • HDL reduces microglia pyroptosis, inhibits TLR4 and NF-κB pathways, and prevents lipid accumulation. • HDL may serve as as a therapeutic strategy for ocular inflammation mediated by CAV-1 expression. Uveitis encompasses a group of intraocular inflammatory diseases that are often associated with low levels of high-density lipoprotein (HDL). The role of HDL in intraocular inflammatory diseases remains unclear. In our research, we established an endotoxin-induced uveitis (EIU) model to investigate the role of HDL. Our study indicated that HDL could suppress ocular inflammation and restore retinal function in EIU mice. Specifically, HDL intervention effectively inhibited microglial activation and promoted the transformation of microglia from the M1 phenotype to the M2 phenotype. Furthermore, HDL intervention reduced microglial pyroptosis. Additionally, HDL was found to inhibit lipid accumulation in LPS-induced microglia, which is associated with inflammation, M1 polarization, and pyroptosis, by enhancing the expression of Caveolin-1 (CAV-1). Finally, we demonstrated that the function of HDL may be partially dependent on CAV-1 expression. We conclude that HDL inhibits pathological ocular inflammation by regulating M1/M2 phenotype polarization and pyroptosis through the modulation of lipid accumulation and CAV-1 expression. This suggests that HDL may represent a novel therapeutic strategy for ocular inflammation.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2024.113592