Lycii Fructus-derived extracellular vesicles-like particles attenuate sodium iodate-induced retinal injury by transporting bioactive cargo molecules

LF-EVLPs treatment ameliorates retinal injury in mice. • LF-EVLPs mitigates oxidative stress, inflammation and complement factors in retinal injury. • LF-EVLPs exert retinal protective effects through the synergistic actions of multiple active ingredients. Oxidative stress and inflammation are major contributors to the development of age-related macular degeneration (AMD), which is one of the retinal degeneration (RD) diseases that are characterized by progressive damage to photoreceptors and retinal pigment epithelium (RPE) cells. This condition can ultimately lead to blindness. Lycii Fructus can clear liver heat, improve vision, and protect the optic nerve. Thus, the aim of this study was to investigate whether nanovesicles derived from Lycii Fructus (LF) can alleviate retinal damage. LF extracellular vesicle-like particles (EVLPs) were isolated from fresh Lycii Fructus . Intravitreal injection of LF-EVLPs resulted in significant retinal protective effects, such as the preservation of RPE cell morphology and junctional integrity, enhanced photoreceptor survival, improved retinal thickness, and restored visual function, in sodium iodate-induced retinal injury mice. Moreover, LF-EVLPs reduced retinal ROS levels and suppressed glial cell activation. Further experiments demonstrated that LF-EVLPs exert neuroprotective effects by modulating the NF-κB signalling pathway and suppressing the aberrant activation of proinflammatory cytokines ( IL-1β and TNF-α ) and complement factors ( C3, C4b, and C5 ). Through an integrated analysis of LF-EVLPs components and the retinal proteome, we identified 12 components and 17 target genes. We confirmed that the active ingredients caffeic acid phenethyl ester (CAPE), a derivative of caffeic acid, and nicotinamide (NAM) exhibit neuroprotective effects in sodium iodate-induced retinal injury mice. Our research provides new insight into neuroretinal protection, for which plant-derived EVLPs may be a promising therapeutic approach. LF-EVLPs preserve the structural and functional integrity of the retina by delivering bioactive constituents and attenuating oxidative stress, modulating the NF-κB pathway, suppressing inflammatory responses, and regulating the complement system after retinal injury. Download: Download high-res image (133KB) Download: Download full-size image