Lin, I.-C. | bioRxiv Science

bioRxiv2024

Innovative platelet-derived extracellular vesicle drug delivery system for the treatment of corneal neovascularization

Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be easily endocytosed owing to their lipid bilayer membrane and nanosized structure, thereby increasing the bioavailability and functionality of their therapeutic effects. PEVs also possess multiple trophic factors that make them effective therapeutic agents. Since nanomedicine offers advantages over traditional therapies for eye diseases by overcoming physical ocular barriers, PEVs combined with an anti-angiogenic agent, kaempferol (KM), were evaluated for their ability to inhibit abnormal vessel formation in the cornea. Characterization of the nanoparticles indicated successful preparation of KM- loaded PEVs (PEV-KM) with a mean diameter of [~]160 nm and an encapsulation efficiency of [~]61%. PEV-KM was efficiently internalized into human vascular endothelial cells, resulting in inhibited function, evidenced by lower wound closure rates, reduced tube formation capacity, and downregulation of angiogenesis-related gene expression. Moreover, prolonged ocular retention was observed followed by topical application of PEV and PEV-KM in mouse eyes. In an alkali-burned corneal neovascularization (CoNV) mouse model, PEV (1%) was found to reduce vessel formation in the injured cornea. PEV with KM (1% PEV with KM 6 {micro}g/mL) showed an even stronger effect in suppressing CoNV and reducing the expression of proangiogenic and inflammatory cytokines. Together, our data suggests that topical administration of PEVs or in combination with KM (PEV-KM) is a promising therapeutic for managing CoNV.

bioengineering↗

bioRxiv2020

Equations governing dynamics of excitation and inhibition in the mouse corticothalamic network

Although cortical circuits are complex and interconnected with the rest of the brain, their macroscopic dynamics are often approximated by modeling the averaged activities of excitatory and inhibitory cortical neurons, without interactions with other brain circuits. To verify the validity of such mean-field models, we optogenetically stimulated populations of excitatory and parvalbumin-expressing inhibitory neurons in awake mouse visual cortex, while recording population activity in cortex and in its thalamic correspondent, the lateral geniculate nucleus. The cortical responses to brief test pulses could not be explained by a mean-field model including only cortical excitatory and inhibitory populations. However, these responses could be predicted by extending the model to include thalamic interactions that cause net cortical suppression following activation of cortical excitatory neurons. We conclude that mean-field models can accurately summarize cortical dynamics, but only when the cortex is considered as part of a dynamic corticothalamic network.

neuroscience↗