Inherited Retinal Dystrophies (IRDs), such as Stargardt’s disease (STGD), lack effective treatments. STGD is characterised by mutations in the ABCA4 gene, leading to lipofuscin accumulation, oxidative stress (OS) and Ca2+ dysregulation, ultimately causing photoreceptor death.
This study evaluates the therapeutic potential of MP-004, a small molecule designed to modulate OS and maintain Ca2+ homeostasis through ocular instillation. Using an acute light-induced photo toxicity mice model (Abca4-/- Rdh8-/-) we demonstrate that MP-004 significantly preserves retinal function. Longitudinal ERGs showed that treated animals maintained significantly higher scotopic and photopic responses compared to controls for at least to 5 months (ongoing study). Furthermore, the study revealed a notable sex-related difference: female mice exhibited lower baseline ERG amplitudes and greater sensitivity to phototoxicity compared to males. These findings support MP-004 as a promising, non-invasive candidate for the functional protection of the retina in STGD and other IRDs.
In recent years scaffolds containing carbon nanotubes (CNTs) have emerged as promising conductive materials to interface with electroactive tissues due to their unique electrical and mechanical properties. The use of patterns, especially hexagonal patterns, has also been proven to improve 3D cell culture environment for in vitro modelling. We designed 3D printable hydrogels with and without CNTs in order to study the effect of both surface pattern and CNT incorporation on electroactive hiPSC-derived neuron and cardiomyocyte differentiation. We found that CNTs and surface topography greatly affects neuronal culture maturation, by improving neuronal marker expression, calcium transient amplitude and axonal network maturation, while cardiomyocyte culture was mainly impacted by CNT presence independently of surface structure. In future experiments a more complex dual-conductive scaffold matrix and structure will be studied. Overall, this study provided insights into the impact of surface structure and composition in electroactive cell differentiation and maturation.