Biology subjects

Marigo, V.

Publications and source records attributed to Marigo, V..

2 recordsLinked to original sources

bioRxiv2024

H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration

Photoreceptor death causes blinding inheritable retinal diseases, such as retinitis pigmentosa (RP). As disease progression often outpaces therapeutic advances, finding effective treatments is urgent. This study focuses on developing a targeted approach by evaluating the efficacy of small peptides derived from pigment epithelium-derived factor (PEDF), known to restrict common cell death pathways associated with retinal diseases. Peptides with affinity for the PEDF receptor, PEDF-R, (17-mer and H105A) delivered via eye drops reached the retina, efficiently promoted photoreceptor survival, and improved retinal function in RP mouse models based on both the rd10 mutation and the rhodopsin P23H mutation. Additionally, intravitreal delivery of AAV-H105A vectors delayed photoreceptor degeneration in the latter RP mouse model. Furthermore, peptide H105A specifically prevented photoreceptor death induced by oxidative stress, a contributing factor to RP progression, in human retinal organoids. This promising approach for peptide eye drop delivery holds significant potential as a therapeutic for preventing photoreceptor death in retinal disorders, offering a high safety profile, low invasiveness and multiple delivery options. One Sentence SummaryNeurotrophic PEDF peptides delivered as eye drops preserve photoreceptor viability, morphology, and function in models of human retinal diseases.

neuroscience↗

bioRxiv2021

Composite solid lipid nanoparticles with hydrogel core for delivering small hydrophilic molecules to the retina: an in vitro study using ARPE-19 and 661W cells

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargo to the retina. The new formulation, based on a gel core and composite shell, allowed up to two times increase in the encapsulation efficiency. The type of hydrophobic polyester used in the composite shell mixture affects the particle surface charge, colloidal stability, and cell internalization profile. We validated the SLN capability as a drug delivery system by performing encapsulation of a hydrophilic neuroprotective cyclic guanosine monophosphate analogue, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with size of {+/-} 250nm, anionic charge > -20 mV, and an encapsulation efficiency value of {+/-}60%, criteria that are suitable for retinal delivery. In vitro studies using ARPE-19 and 661W retinal cell lines revealed a relatively low SLN toxicity, even when high particle concentration was used. More importantly, SLN could be uptaken by the cells and the release of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings suggest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all characteristics suitable for drug delivery of small hydrophilic active molecules into retinal cell.

neuroscience↗