Polyphenol-based self-assembled nanoparticles treating uveitis by inflammation-oxidative stress suppression.

Area of Science:

• Ophthalmology
• Immunology
• Nanomedicine

Background:

• Uveitis causes vision loss via blood-retinal barrier (BRB) breakdown and inflammation.
• Microglia activation, reactive oxygen species (ROS), and cytokine storms exacerbate BRB dysfunction.
• Epigallocatechin gallate (EGCG) scavenges ROS, while metformin (MET) inhibits inflammation.

Purpose of the Study:

• To develop multifunctional nanoparticles (EM NPs) combining EGCG and MET for synergistic uveitis treatment.
• To investigate the therapeutic effects of EM NPs on microglial polarization and BRB integrity.
• To evaluate the efficacy of EM NPs in experimental autoimmune uveitis (EAU) models.

Main Methods:

• Constructed self-assembling multifunctional nanoparticles (EM NPs) encapsulating EGCG and MET.
• Assessed EM NP effects on microglial phenotype (M1/M2 polarization) and NF-κB signaling.
• Evaluated EM NP impact on ROS levels, apoptosis, tight junction proteins, and BRB integrity.
• Utilized experimental autoimmune uveitis (EAU) rat models to assess therapeutic outcomes.

Main Results:

• EM NPs promoted M2 microglial polarization and suppressed pro-inflammatory cytokines by inhibiting NF-κB.
• EM NPs reduced ROS, inhibited mitochondrial apoptosis, and preserved tight junction proteins in retinal pigment epithelial (RPE) cells.
• EM NP treatment significantly improved retinal and choroidal perfusion in EAU rat models.
• Demonstrated synergistic protective effects on the BRB, mitigating uveitis-induced damage.

Conclusions:

• EM NPs represent a promising therapeutic strategy for uveitis management.
• The combination of EGCG and MET in nanoparticles offers synergistic benefits for BRB protection.
• This approach holds potential for novel treatments targeting inflammatory and oxidative damage in ocular diseases.